Coronary ectasia in Takayasu's arteritis.
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Coronary Angiography↗
Biomedical subjects
H Yoshimura
Publications and source records attributed to H Yoshimura.
Tetanization during GABAA receptor activation induces long-term depression in visual cortex slices.
In rat visual cortex slices, long-term depression of synaptic transmission was induced by tetanic stimulation to white matter during bath-application of the GABAA agonist muscimol. This result supports the view that a combination of presynaptic activity and postsynaptic inhibition leads to a depression of synaptic efficiency.
Animals↗
Bronchial epithelial cells of patients with asthma release chemoattractant factors for T lymphocytes.
BACKGROUND: T lymphocytes may orchestrate the inflammatory response in atopic asthma, but the mechanisms that promote T-cell accumulation in asthmatic airways are still unclear. In this study, we tested the hypothesis that bronchial epithelial cells of patients with atopic asthma release chemoattractant factors for T lymphocytes. METHODS: Sixteen patients with atopic asthma and eight healthy control subjects were selected for this study. Bronchial epithelial cells were isolated from biopsy specimens obtained by means of bronchoscopy and cultured for 48 hours in serum- and hormone-free medium, with or without 10(-6) mol/L histamine. RESULTS: Only the supernatants of cells from donors with asthma showed chemotactic activity for T lymphocytes, and this was significantly increased (p < 0.025) by exposure to histamine. Chemotactic activity was in part mediated by interleukin-8 (IL-8), because an antibody against human IL-8 significantly reduced it (p < 0.05) and the cell supernatants contained appreciable amounts of immunoreactive IL-8 (0.89 +/- 0.39 ng/ml). Both the residual chemotactic activity of unstimulated epithelial cells and the increased activity caused by histamine were mediated by a single protease-sensitive substance with an apparent molecular weight of 56,000 d and an estimated isoelectric point of 8.8 to 9.1. The partially purified chemoattractant specifically enhanced the migration of CD4+ T lymphocytes, and its activity was inhibited by the univalent Fab fragment of a monoclonal antibody against CD4. CONCLUSION: These results extend our previous observations, indicating an important effector role of bronchial epithelium in asthma.
Adult↗
Three-dimensional structure of F1-ATPase of thermophilic bacterium PS3 obtained by electron crystallography.
The three-dimensional molecular structure of the F1-ATPase from a thermophilic bacterium PS3 (TF1) at 3 nm resolution was reconstructed from a series of tilted, negatively stained electron microscopic images of two-dimensional crystals which were formed on a clean surface of mercury. It was shown that six ellipsoidal columns, each approximately 7 nm in length and approximately 3 nm in diameter, corresponding to the alpha and beta subunits, surrounded a central hollow cavity of approximately 2.8 nm in diameter. The cavity, however, did not penetrate the molecule, and a mass, most likely the gamma subunit, existed in the cavity at a depth of approximately 3.4 nm from the top.
Bacteria↗
Differentiation of Erysipelothrix rhusiopathiae and Erysipelothrix tonsillarum by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of cell proteins.
The protein patterns of whole cells of Erysipelothrix rhusiopathiae and Erysipelothrix tonsillarum were studied by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The protein patterns of the 16 strains of E. rhusiopathiae and E. tonsillarum studied, including the type strains of these two species, resembled each other, except that there were 71-, 41-, 34-, and 26-kDa proteins in the E. rhusiopathiae pattern and 74-, 44-, 36-, and 25-kDa proteins in the E. tonsillarum pattern. This observation indicates that there is some phenotypic heterogeneity in the genus Erysipelothrix. In addition, the protein patterns of E. rhusiopathiae serotype reference strains representing serotypes 1 through 23 and type N were compared. The protein patterns of serotype 1a, 1b, 2, 4, 5, 6, 8, 9, 11, 12, 15, 16, 19, and 21 and type N strains were similar to the pattern of the type strain of E. rhusiopathiae (strain ATCC 19414). Conversely, the protein patterns of serotype 3, 7, 10, 14, and 20 strains were very similar to the pattern of the type strain of E. tonsillarum (strain ATCC 43339). An atypical pattern was observed in serotype 13, 17, 18, 22, and 23 strains. These results suggest that this method may be used as an aid in studying the taxonomy of these bacteria.
Animals↗
Clinical experience with an advanced laser digitizer for cost-effective digital radiography.
Film digitization has not been widely pursued in clinical settings mainly because of perceived limitations involving film latitude and image quality. However, a high-quality laser digitizer can be combined with wide-latitude film and specially developed digital processing techniques to achieve image quality comparable or superior to that of storage phosphor computed radiography (SPR) over a wide range of exposure. This film digitization system provides the operational advantages of digital radiography, such as consistent image density, high-quality inexpensive duplicates, and digital storage and retrieval capability. The reliability and monetary costs of the system also compare favorably with those of SPR. In the long term, technologies that employ reusable plates and do not require chemical processing to produce diagnostic images may well replace screen-film systems. Presently, however, film digitization remains a practical and cost-effective approach to digital radiography.
Cost-Benefit Analysis↗
In vitro metabolic formation of a new metabolite, 6 beta-hydroxymethyl-delta 9-tetrahydrocannabinol from cannabidiol through an epoxide intermediate and its pharmacological effects on mice.
The oxidative metabolism of cannabidiol (CBD) at the 8,9-double bond was examined. 8R,9-Epoxy-CBD was identified by GC-MS as a new metabolite of CBD produced by hepatic microsomal fractions of guinea pigs, rats and mice. The reaction required NADPH as a cofactor and molecular oxygen. The optimal pH for the reaction was 7.4-8.0. The 8R,9-epoxy-CBD forming activity was highest in guinea pigs, followed by mice and rats in the presence of 3,3,3-trichloropropene-1,2-oxide (TCPO), an inhibitor of epoxide hydrolase. The activity was significantly suppressed by SKF 525-A, alpha-naphthoflavone, metyrapone and carbon monoxide. 8R,9-Epoxy-CBD was further converted to 6 beta-hydroxymethyl-delta 9-tetrahydrocannabinol (6 beta-CH2OH-delta 9-TCH) and 8,9-dihydro-8,9-dihydroxy-CBD by hepatic microsomes of guinea pigs, rats and mice. Microsomal formation of 6 beta-CH2OH-delta 9-THC was markedly increased in the presence of TCPO with a concomitant decrease in the formation of 8,9-dihydro-8,9-dihydroxy-CBD in all animal species examined. Furthermore, 6 beta-CH2OH-delta 9-THC was also identified as a new metabolite of CBD produced by hepatic microsomes of guinea pigs. 6 beta-CH2OH-delta 9-THC exhibited THC-like pharmacological effects, catalepsy, analgesia, pentobarbital-induced sleep prolongation and hypothermia in mice, although these effects were less marked than those of delta 9-THC. This study presents the first example of the biotransformation of CBD to a delta 9-THC derivative which exhibits some pharmacological effects.
Analgesics↗
Formation of p-hydroxycocaine from cocaine by hepatic microsomes of animals and its pharmacological effects in mice.
The hepatic microsomal metabolism of cocaine and the pharmacological effects of some metabolites were studied in experimental animals. Hepatic microsomes from mice, rats and guinea pigs catalyzed the oxidation of cocaine to m- and p-hydroxycocaines. Only trace amounts of m-hydroxycocaine were detected in the extract of the incubation mixture with rabbit hepatic microsomes. The total amount of the two hydroxycocaines was less than 12% that of norcocaine which was the most predominant microsomal metabolite in all the animals species examined. The administration of p-hydroxycocaine (20 mg/kg i.p.) to mice significantly increased locomotor activity (total distance and number of rearing movements). The effect of p-hydroxycocaine was more active or comparable with that of cocaine, indicating that this metabolite is an active metabolite of cocaine.
Animals↗
Suppression of liver microsomal drug-metabolizing enzyme activities in adult female rats pretreated with cannabidiol.
The suppression by cannabidiol (CBD) of the liver microsomal drug-metabolizing enzyme activities in female rats was demonstrated and its mechanism was examined. Pretreatment of rats with CBD (10 mg/kg, i.p.) caused temporary decreases in contents of cytochrome P450 (P450) and b5 and NADPH-cytochrome c (P450) reductase activity compared with values from the vehicle control group. p-Nitroanisole O-demethylase, aniline hydroxylase, d-benzphetamine N-demethylase and delta 9-tetrahydrocannabinol 11-hydroxylase were also decreased by the CBD pretreatment. The latter two activities took a longer time to return to control levels than the former two. However, the CBD pretreatment, which reduced the protein level of P450 UT-2 (CYP2C11) in adult male rats, did not decrease the protein level of P450 F-1 (CYP2C6) or F-2 (CYP2C12) in liver microsomes from female rats. These results suggest that the mechanisms by which CBD suppresses liver microsomal drug-metabolizing enzyme activities are different in male and female rats.
Animals↗
Purification and characterization of a morphine UDP-glucuronyltransferase isoform from untreated rat liver.
A morphine UDP-glucuronyltransferase was purified from liver microsomes of untreated Sprague-Dawley rats. A new gel, omega(beta-carboxypropionylamino)octyl Sepharose 4B, was prepared by coupling monomethylsuccinate with omega-aminooctyl Sepharose 4B and this was used as an efficient tool for the separation of microsomal enzymes. Emulgen 911 solubilized microsomes were applied to a column packed with the gel and eluted at pH 7.4 while increasing KCl concentration in a stepwise manner. An isoform was further purified with UDP-hexanolamine Sepharose 4B gel. The purified UDP-glucuronyltransferase (morphine UGT of untreated rat, morphine UGTUT) exhibited a molecular weight of 52000 on sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis and was capable of glucuronidating the 3-hydroxyl group of morphine. The isoform catalyzed to a small extent the glucuronidation of 4-hydroxybiphenyl; however, no glucuronidation activity towards androsterone, testosterone, bilirubin, 4-nitrophenol and the 6-hydroxyl group of morphine was observed. The difference in properties, compared with morphine UGT (molecular weight 56000) which was purified previously from phenobarbital-treated rats, is discussed.
Animals↗
Metabolic formation of dimethylamine and methylamine from basic drugs containing N-methyl group: a newly established chromatographic assay and its application to the determination of deaminase activity.
A new method of assaying deaminase activity was established in which methylamine and/or dimethylamine formed from drugs containing N,N-dimethyl or N-methyl group were derivatized with phenylisothiocyanate to phenylthiourea derivatives. After purification with Sep-PAK C18 cartridge, the derivatives were separated by a reversed phase high-performance liquid chromatography monitored by ultraviolet absorption. The recoveries and determination limits of methylamine and dimethylamine were over 55% and about 0.4 nmol/ml of incubation mixture, respectively. The method was used to measure the deaminase activities of liver microsomes of rats, rabbits and guinea pigs for 11 drugs. Of the compounds tested, diphenhydramine and diltiazem are deaminated with microsomes from all the above animal species; rat and rabbit liver microsomes also well deaminated promethazine. Most other drugs such as chlorpromazine, promazine, imipramine, amitriptyline and tetracaine were found to be poor substrates. In general, dimethylamine but not methylamine was the predominant metabolite formed from drugs containing N,N-dimethylamino group. The results also suggested that the deamination of these compounds takes place mainly via a one step mechanism, thus implying that the sequential reaction consisting of N-demethylation and elimination of ammonia is of minor importance. The relation between in vitro deaminase activity and the extent of the in vivo deamination for drugs is discussed.
Aminohydrolases↗
Identification of in vitro metabolites of 2,4,6,2',4',6'-hexachlorobiphenyl from phenobarbital-treated dog liver microsomes.
We studied in vitro metabolites of 2,4,6,2',4',6'-hexachlorobiphenyl (HCB, IUPAC PCB No. 155) produced by liver microsomes of a phenobarbital (PB)-treated beagle dog. The major metabolites were 3-hydroxy-2,4,6,2',4',6'-HCB (M-1), 4-hydroxy-2,6,2',4',6'-pentachlorobiphenyl (PenCB, M-2) and 3,4-dihydroxy-2,6,2',4',6'-PenCB (M-3). Furthermore, 4-hydroxy-2,3,6,2',4',6'-HCB (M-4), which could be formed via the 3,4-epoxidation and the subsequent NIH-shift of the chlorine from the 4 to the 3 position, was also detected. We found that M-3 is a common secondary metabolite of the two major monohydroxy metabolites, M-1 and M-2. These results indicate that the dog seems to metabolize and eliminate this congener not only by a mechanism involving direct insertion of a hydroxyl group but also via an arene oxide intermediate.
Animals↗
Cytochrome P450 isozymes catalyzing the hepatic microsomal oxidation of 9-anthraldehyde to 9-anthracene carboxylic acid in adult male rats.
Microsomal aldehyde oxygenase (MALDO) activity for 9-anthraldehyde (9-AA) was significantly higher in the male than in the female adult rat liver. 9-AA MALDO activity was also significantly enhanced by pretreatment with dexamethasone and phenobarbital, whereas it was not significantly changed by 3-methylcholanthrene or acetone. Several cytochrome P450 isozymes purified from rat hepatic microsomes were able to catalyze the oxidation of 9-AA to 9-anthracene carboxylic acid (9-ACA) in the presence of NADPH, NADPH-cytochrome P450 reductase and dilauroylphosphatidylcholine. Under the ordinary conditions of the reconstituted system, the catalytic activities (nmol/min/nmol P450) of cytochrome P450s, 2A1, 2B2, 2C6, 2C11 and 3A2 were 1.53 (1.37 in the presence of cytochrome b5), 1.20 (2.06), 4.87 (7.75), 18.0 (21.6) and 0.90 (1.17), respectively. Cytochrome P450 2C11 (CYP 2C11) showed the highest catalytic activity of the cytochromes examined. In the reconstituted system using the lipids extracted from microsomes, CYP 3A2 more effectively catalyzed the oxidation of 9-AA to 9-ACA, and its catalytic activity (nmol/min/nmol P450) was 3.33 or 6.61 in the absence or presence of cytochrome b5, respectively. The antibody against CYP 2C11 inhibited by 90% the hepatic microsomal oxidation of 9-AA MALDO activity in adult male rats, but the activity was not inhibited by antibody against CYP 3A2. These results show that the individual forms of cytochrome P450 have a catalytic activity for the oxidation of 9-AA to 9-ACA, and that CYP 2C11 is the major constitutive catalyst of 9-AA MALDO activity in untreated adult male rat liver.
Animals↗
Effective prevention of ischemic injury of the dearterialized canine liver by FK506 pretreatment.
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Adenosine Triphosphate↗
[Effects of cyclophosphamide on spontaneous testicular and pancreatic lesions in WBN/Kob rats].
This study was undertaken to investigate the effects of cyclophosphamide (CP) on spontaneous pancreatitis and testicular atrophy of WBN/Kob rats. CP was given daily in drinking water to groups of 20 male 6-week-old WBN/Kob rats at doses of 0 (control), 1.25 or 2.5 mg/kg for 20 weeks. The final body weight in the 2.5 mg/kg CP group was significantly lower than that in the control group. There were no significant differences in blood glucose levels and weights of the pancreas and testis between groups. On histopathological examinations, pancreatitis and testicular atrophy were noted in each group. However, the incidence of pancreatitis characterized by inflammatory cell infiltration and fibrosis in the 2.5 mg/kg CP group was significantly decreased as compared to the control group. In contrast, testicular atrophy was more severe in the 2.5 mg/kg CP group than in the control group. Thus the results demonstrated that CP has inhibitory effects on the development of pancreatitis and enhancing effects on the development of testicular atrophy in WBN/Kob rats.
Administration, Oral↗
The antimicrobial activity in vitro of cefpirome and 6 other beta-lactam antibacterial agents against clinical isolates.
The in vitro activity of cefpirome (CPR) was compared with that of cefazolin (CEZ), cefotiam (CTM), flomoxef (FMOX), cefotaxime (CTX), ceftazidime (CAZ) and imipenem/cilastatin (IPM/CS) against 384 clinical isolates, for tested by the both microdilution method. The activity of CPR against Staphylococcus aureus (MIC50, 1 microgram/ml) and Enterococcus faecalis (MIC50, 8 micrograms/ml) was better than CTX and CAZ, but slightly less than IPM/CS. CPR and other antibacterial agents were not effect against methicillin resistant S. aureus and Enterococcus faecium. The activity of CPR against Enterobacteriaceae was as good as that of CTX, CAZ, and IPM/CS, and more effective than CEZ, CTM and FMOX. The MIC50 of CPR for Acinetobacter calcoaceticus (2 micrograms/ml) and the MIC50 of CPR for Pseudomonas aeruginosa (8 micrograms/ml) were as good as that of CAZ. Conclusionly, CPR was a new broad spectrum cephalosporin as compared with used cephalosporins.
Anti-Bacterial Agents↗
Purification and characterization of a novel 46.5-kilodalton esterase from mouse hepatic microsomes.
A novel membrane-bound esterase was purified from mouse hepatic microsomes. The purified protein (ES46.5K) showed a single protein-staining band on sodium dodecyl sulfate-polyacrylamide gel with a minimum molecular weight of 46.5 Kdalton. ES46.5K possessed esterase activity toward 11-acetoxy-delta 8-tetrahydrocannabinol (11-OAc-delta 8-THC) (27.1 mumol/min/mg protein) and p-nitrophenylacetate (119 mumol/min/mg protein), and these activities were 38 and 47 times, respectively, as high as those of microsomes. The N-terminal amino acid sequence of the protein was as follows: G-K-T-I-S-L-L-I-S-V-V-L-V-A-Y-Y-L-Y-I. This sequence has no homology to those of the known carboxylesterases, indicating that this enzyme is a novel type of esterase bound to the microsomal membrane.
Amino Acid Sequence↗
[Inducing ability of co-planar PCBs toward bilirubin UDP-glucuronyltransferase of liver microsomes: the remarkable difference between guinea pigs and rats].
The induction of liver microsomal UDP-glucuronyltransferase (UGT) activity toward bilirubin by pretreatment with 3, 4, 3', 4'-tetrachlorobiphenyl (TCB), 3, 4, 5, 3', 4'-pentachlorobiphenyl (PenCB) and 3-methylcholanthrene (MC) was studied in guinea pigs and rats. In addition, microsomal benzo(a)pyrene 3-hydroxylase and cytosolic DT-diaphorase activities were also measured for the comparison. All of the PenCB, TCB and MC significantly induced the bilirubin UGT activity of guinea pig liver microsomes. The highest induction (6-fold over the control) was seen in the PenCB-treated animal, and MC (3.2-fold) and TCB (2.4-fold) were less effective. On the other hand, the induction of benzo(a)pyrene 3-hydroxylase and DT-diaphorase activities of guinea pigs was not so remarkable as that of bilirubin UGT activity. In the guinea pig, the inducibility of bilirubin UGT activity seemed to be correlated with the toxicity induced with PenCB, TCB and MC. In contrast to the guinea pig, UGT activity toward bilirubin in the rat was significantly decreased by the treatment with the inducers described above. These results suggest that bilirubin UGT activity in the guinea pig can be an index for the toxicity of polychlorinated biphenyls as like as benzo(a)pyrene 3-hydroxylase and DT-diaphorase activities in the rat.
Animals↗