Inhibitors of prostaglandin biosynthesis from Mucuna birdwoodiana.
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Biomedical subjects
Publications and source records attributed to M Shibuya.
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To elucidate the histopathological features of the middle ear mucosa in otitis media with effusion (OME), 33 specimens were obtained from OME patients (28 from children and 5 from adults) at the time of the ventilation tube insertion, and examined by light- and electron-microscopy. The mucosa from both pediatric and adult OME patients with glue effusion consisted mostly of non-ciliated cells containing numerous low electron-dense granules with or without a core, and many macroapocrine sections were observed on the apical surface of the cells. The mucosa with mucoid effusion showed various secretory activity, but macroapocrine secretions were rarely found. The intercellular space was intact and the junctional complex was well preserved. In serous otitis cases, the epithelia consisted mostly of cuboid ciliated cells and non-ciliated cells without definite secretory activity. But the intercellular space became widened and the junctional complex was occasionally damaged, indicating that the epithelium was quite permeable. We concluded that there was no significant histopathological difference between the OME mucosa of children and that of adults, although the nature of the effusion was closely correlated with the morphological features of the epithelial linings.
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In vivo voltammetry is an electrical detection method by which dopamine and serotonin metabolism can be estimated in the brain of animals. In the present report preliminary and basic experiment were performed before its application to ischemic brain. Firstly, using voltammetry DPV-5 system in vitro, concentration/amplitude curve was obtained with various concentration of 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) diluted in phosphate buffer (pH 7.4). DOPAC appeared at +150 mV (peak 2) while 5-HIAA appeared at +300 mV (peak 3). A linear relation was obtained in the concentrations ranging 5 x 10(-6)-10(-4) M for DOPAC and 10(-6)-10(-4) M for 5-HIAA. While a delay in oxidation potential was noticed for both peaks 2 and 3 by about 30 mV when the pH of solution was decreased by 1. Secondly the DPV-5 system was applied in vivo to the rat striatum. Peak 2 was observed at +150 mV which was increased by intraperitoneal injection of haloperidol, a dopamine receptor blocker and decreased by pargyline, a monoamine oxidase inhibitor. While peak 3 was observed at +300 mV and increased after probenecid and decreased by pargyline, which suggest that peak 2 and 3 correspond to DOPAC and 5-HIAA respectively. Thirdly DPV-5 system was applied to the rat striatum and rat's heart was arrested by KCl injection as a model of extreme brain ischemia. Shortly after cardiac arrest the heights of peak 2 was significantly increased to 600-900% while the increase of peak 3 was not significant, both of which subsided gradually toward 30 minutes after arrest.(ABSTRACT TRUNCATED AT 250 WORDS)
We studied chromosome 22 breakpoints in 24 Philadelphia (Ph1)-positive leukemias. Nineteen of 21 patients with chronic myelogenous leukemia (CML) possessed a chromosomal break within the 5.8 kilobase (kb) breakpoint cluster region (bcr). Furthermore, in one of three cases of acute lymphocytic leukemia (ALL), we found a chromosomal rearrangement in the bcr locus. No chromosomal rearrangements were found in two cases of CML and two cases of ALL using several restriction enzymes. The bcr rearrangement is highly specific for CML. Further analyses will be necessary to determine whether some cases without bcr rearrangement have another specific locus of rearrangement. Two of three cases of CML with blastic crisis had rearrangement of the immunoglobulin gene and T-cell receptor gene. One CML patient with blastic crisis, who achieved complete remission but relapsed thereafter, was found to have the same immunoglobulin gene rearrangement in the blastic crisis and relapse phases, suggesting that the same clone was involved in both crisis and relapse.
We have isolated a human genomic DNA (designated human frt) cross-hybridizing with the v-ros oncogene of UR2 sarcoma virus. Sequencing analysis of this fragment revealed that this sequence contains a 123-base-pair exon-like structure surrounded by consensus sequences of splice acceptor and donor sites. The deduced amino acid sequence of this stretch was highly homologous to a portion of a tyrosine kinase domain of src family. The human frt sequence was found to be conserved in a wide variety of vertebrates. By using a human-mouse hybridoma panel, human frt was located on chromosome 13, while human c-ros-1 was located on chromosome 6.
We have regionally localized the two human tyrosine kinase proto-oncogenes, c-ros-1 and flt, by in situ hybridization. The c-ros-1 has been mapped to 6q22 and the flt to 13q12.
The antimetastatic effects of defibrinogenation with batroxobin were investigated in normal mice and in mice with depressed or activated natural killer (NK) cell activity. Batroxobin inhibited the formation of lung metastases after intravenous inoculation of the F10 subline of B16 melanoma. Inhibition of NK activity by treatment of mice with anti-asialo GM1 antibody abrogated the antimetastatic effects of Batroxobin. Conversely, augmentation of NK cell activity by poly I:C plus treatment with batroxobin produced additive antimetastatic effects. Studies on the mechanism of interaction between Batroxobin and NK cells revealed that Batroxobin treatment did not affect splenic NK activity in vitro. From these data, it was found that the antimetastatic effects of batroxobin are dependent on the level of NK activity in the host.
Cell-mediated immunity of the aging and immune response in the family of gastric cancer have been investigated and the following results were obtained. Immune response particularly of cell-mediated immunity was found decreased in paralled with aging; decreases in peripheral lymphocyte and T-cell counts, rate of Con A and PHA induced blastoid transformation, and the tendency of increase in suppressor T-cell were noted. Investigations on the immune response in the family of gastric cancer revealed that cell-mediated immune response was recreased in the compared to age-matched healthy volunteers. These findings suggest that latent immunological failure may exist in the above family.
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HA1077, but not the potent calcium entry blocker nicardipine reversed experimental chronic cerebral vasospasm induced in a two-hemorrhage canine model. The i.a. administration of HA1077 produced significant increases in vertebral blood flow in dogs. The effects of HA1077 on the vascular responses were studied in vitro. Spiral strips of rabbit aorta were mounted for isometric tension recording in physiological salt solution. HA1077 produced a competitive inhibition of the Ca++-induced contraction of the depolarized rabbit aorta. The pA2 of HA1077 for the Ca@-induced contraction was 6.71. The inhibitory effect of HA1077 on the KCl-induced contraction was not altered by atropine, propranolol, theophylline or indomethacin. HA1077 (10(-8) to 10(-4) M) inhibited contractile responses to KCl, phenylephrine (PHE) and prostaglandin (PG) F2 alpha similarly, whereas verapamil, diltiazem and nicardipine were much less effective in blocking the contractions induced by PHE or PG. Even in Ca++-free physiological salt solution, both PHE and PG were capable of contracting the aorta. These Ca++-free contractile responses to PHE and PG were antagonized effectively by HA1077. Verapamil failed to inhibit these contractions. We also investigated the effects of HA1077 on guinea pig heart contractility. In contrast to calcium entry blockers (which are known to have a direct negative inotropic effect), HA1077 did not change the developed tension in the left atrium at concentrations up to 3 X 10(-4) M. The present evidence demonstrates that the novel antivasospasm drug HA1077 is a class of calcium antagonists different from the calcium entry blockers.
Although present day progressive respiratory management has decreased the tetanus mortality rate, tetanus-related autonomic overactivity remains a lethal condition. The cause, pathophysiology, and treatment of this condition are controversial and no animal model has ever been reported. So we tried to make a rabbit model of this condition. At first we injected 30 micrograms of purified tetanus toxin intravenously. Blood pressure oscillation occurred, but the degree of oscillation was smaller than that was seen in the clinical cases. The degree of oscillation had not changed by addition of 30 micrograms purified toxin 12 hours after first injection. Secondly, 7 days before the experiment we injected 0.5 micrograms of purified tetanus toxin intravenously. On the experiment day, we injected 30 micrograms of purified toxin again. By this method there occurred blood pressure oscillation as same as that was seen in the clinical cases. But no rabbits progressed to circulatory collapse by purified toxin. Then to the last group of rabbits, we injected crude tetanus toxin for purified toxin. The degree of blood pressure oscillation was same as that of cases in which purified toxin was injected, and all rabbits progressed to circulatory collapse.
Hemin-thiolate complexes, as chemical models for cytochrome P-450 monooxygenases, have been shown to cause strand scission of DNA. Circular super-coiled DNA was degraded to open-circular and linear forms by these complexes in 30 min at pH 7.8 under aerobic conditions, the degradation depending on the structure of the thiol ligand and the ratio of thiol ligand to hemin concentration. The relationship between the structure of the thiol ligand and DNA strand cleaving activity was examined. Complete cleavage of DNA was observed by complexes containing TGE and ME at 400-600 moles excess of thiol ligand to hemin, those containing Cys, CysMe, and CysEt at 50-200 moles excess, and those containing MPG, GSH, penta- and nona-peptides at 5-20 moles excess. Complexes containing NACys and MEA caused no cleavage of DNA. Inhibition experiments suggested the involvement of active oxygen species in the cleavage.
DL-[14C]Leucine or L-[3H]leucine was injected intraperitoneally into pyridoxine-deficient and control rats, and the subsequent incorporation of the radioactivities into aspartate aminotransferase (AspAT) isozymes and the total soluble protein in the liver was measured. AspAT in the cytosol (AspATc) was separated into 3 subfractions with different characteristics on chromatofocusing. The results showed that in the liver of pyridoxine-deficient rats, the syntheses of all 3 subfractions of AspATc and degradation of AspATc (total) were increased, but that the syntheses and degradation of the total soluble protein and mitochondrial AspAT (AspATm) were not much different from those in control rats. The half-lives of soluble protein and AspATm were calculated to be 3.26-3.72 and 5.02-6.67 days, respectively, in both groups, and that of AspATc in control liver was found to be 4.78 days. The rate of degradation of AspATc in pyridoxine-deficient rat liver could not be calculated, because its kinetics were very complicated; there were apparently at least 2 components with different rates of degradation. Thus pyridoxal 5'-phosphate (PLP) apparently affects both the synthesis and degradation of AspATc, but does not affect the turnover of AspATm in rat liver.