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Biomedical subjects

H Yoshimura

Publications and source records attributed to H Yoshimura.

At least 217 records · Page 12Linked to original sources
PubMed1993

[A case of subacute thyroiditis with highly positive thyrotropin receptor antibodies and normal radioiodine uptake].

In this paper, we report on a 40-year-old female with subacute thyroiditis (SAT) who showed high levels of TSH-binding inhibitory immunoglobulins (TBII) and thyroid-stimulation blocking antibodies (TSBAb) from the early stage of the disease. Thyrotoxicosis continued for 2 months and it was subsequently followed by severe hypothyroidism. Levothyroxine was then started. At that time, both TBII and TSBAb were still positive, but they disappeared 6 months later and she remained euthyroid thereafter without treatment. When she was in a thyrotoxic phase and had a suppressed TSH level, her 24-hour radioiodine uptake was not suppressed (11%), and thyroid scan showed partial suppression of uptake in the right lobe. These observations indicate that the presence of TSH receptor antibodies (TRAb) may have modified the changes in thyroid state and the course of SAT.

Adult↗
PubMed1993

A cytochrome P450 isozyme having aldehyde oxygenase activity plays a major role in metabolizing cannabinoids by mouse hepatic microsomes.

A cytochrome P450 (designated P450 MUT-2) which catalyses the oxidation of 11-oxo-delta 8-tetrahydrocannabinol (11-oxo-delta 8-THC) to delta 8-THC-11-oic acid has been purified from hepatic microsomes of untreated male mice. Analysis of NH2-terminal sequence suggests that the isozyme is a member of the P450 2C gene subfamily. P450 MUT-2 exhibited aldehyde oxygenase activity for 11-oxo-delta 8-TH, 11-oxo-delta 9-THC, 11-oxo-cannabinol (11-oxo-CBN) and 9-anthraldehyde together with high activity for the hydroxylation of cannabinoids at the 11-position. Antibody against P450 MUT-2 significantly inhibited the microsomal formation of delta 8-THC-11-oic acid from 11-oxo-delta 8-THC, but not that of 9-anthracene carboxylic acid from 9-anthraldehyde. Major metabolic reactions of delta 8-THC, delta 9-THC and CBN with mouse hepatic microsomes were the 11-hydroxylation (all cannabinoids), 7 alpha-(delta 8-THC) or 8 alpha-hydroxylation (delta 9-THC) and epoxide formation (delta 8- and delta 9-THC). All these reactions except for 7 alpha-hydroxylation of delta 8-THC and alpha-epoxide formation from delta 9-THC were also markedly inhibited by the antibody. These results indicate that P450 MUT-2 is a major enzyme for metabolizing cannabinoids by mouse hepatic microsomes.

Animals↗
PubMed1993

Reduced Mg2+ block of N-methyl-D-aspartate receptor-mediated synaptic potentials in developing visual cortex.

Molecular cloning has demonstrated a diversity of artificially expressed N-methyl-D-aspartate (NMDA) receptors, implying a similar diversity of naturally occurring NMDA receptors in situ. Particularly significant was the success in expression of NMDA receptor classes exhibiting various sensitivities to Mg2+ block, a voltage-dependent channel blockade by Mg2+ that is essential to NMDA receptor functioning. Release from Mg2+ block often allows or facilitates the occurrence of long-term potentiation, a form of synaptic plasticity. Here we show that in the immature visual cortex, which is more susceptible to long-term potentiation than adult visual cortex, synaptically activated NMDA receptors, unlike those in the adult, have varying but clearly reduced sensitivities to Mg2+ block. We propose that the initially expressed, later-eliminated NMDA receptors exhibiting a reduced Mg2+ block may underlie the greater susceptibility to plasticity in the immature neocortex.

Age Factors↗
PubMed1993

Facilitatory effects of substance P on the susceptibility to long-term potentiation in the visual cortex of adult rats.

We studied whether substance P (SP) facilitates induction of long-term potentiation (LTP) in adult rat visual cortex slices, using intracellular recordings of postsynaptic potentials (PSPs) elicited by white matter stimulation. Tetanic stimulation in normal medium induces no change of the PSP amplitude. In SP-containing medium, by contrast, tetanization potentiated the PSP amplitude in 5 over 7 cells examined. Although the other 2 cells underwent no change, the overall effect of SP was an increase in the probability of LTP induction. This effect of SP was canceled out by bath-application of the non-peptide antagonist CP96,345 (n = 7) or intracellular application of guanosine 5'-beta-thio-diphosphate (GDP beta S; n = 7). These results suggest that SP increased LTP susceptibility of neurons in the adult rat visual cortex through SP receptor-mediated mechanisms.

2-Amino-5-phosphonovalerate↗
PubMed1993

Transient increase in endogenous basic fibroblast growth factor in neurons of ischemic rat brains.

An antiserum against basic fibroblast growth factor (bFGF) was shown to recognize an 18-kDa protein (possibly bFGF) in crude neocortical extracts by immunoblot and used to investigate the changes of bFGF immunoreactivity in neurons and astrocytes of the cerebral cortex of rats 1-21 days after unilateral occlusion of the middle cerebral artery (MCA). The mildly ischemic neocortex exhibited no signs of cell loss or degeneration in Nissl-stained sections 1-14 days after MCA occlusion, but it contained pyramidal cell bodies and processes with more intense bFGF immunoreactivity than did the control neocortex. bFGF immunoreactivity in the ischemic hemisphere gradually declined in intensity and by 21 days after MCA occlusion, it had reached the control level. On the other hand, there were many bFGF immunoreactive astrocytes in the primary olfactory cortex on the side of infarction. These findings suggest that MCA occlusion causes an increase in bFGF content not only in astrocytes but also in neurons, depending on the severity of the ischemic insult in individual cortical regions. The transient augmentation of bFGF expression or accumulation in mildly ischemic pyramidal neurons but not in astrocytes is in line with previous studies suggesting the neurotrophism of exogenously applied bFGF.

Animals↗
PubMed1993

The pharmacokinetics of primaquine in calves after subcutaneous and intravenous administration.

The pharmacokinetics of primaquine was studied in calves of 180-300 kg live weight. Primaquine was injected at 0.29 mg/kg (0.51 mg/kg as primaquine diphosphate) intravenously (IV) or subcutaneously (SC) and the plasma concentrations of primaquine and its metabolite carboxyprimaquine were determined by high-performance liquid chromatography. The extrapolated concentration of primaquine at zero time after IV administration was 0.50 +/- 0.48 microgram/ml (mean +/- SD) which decreased with an elimination half-life of 0.16 +/- 0.07 h. Primaquine was rapidly converted to carboxyprimaquine after either route of administration. The peak concentration of carboxyprimaquine was 0.50 +/- 0.08 microgram/ml at 1.67 +/- 0.15 h after IV administration. The corresponding value was 0.47 +/- 0.07 micrograms/ml at 5.05 +/- 1.20 h after SC administration. The elimination half-lives of carboxyprimaquine after IV and SC administration were 15.06 +/- 0.99 and 12.26 +/- 3.06 h, respectively. The areas under the concentration-time curve for carboxyprimaquine were similar following either IV or SC administration of primaquine; the values were 11.85 +/- 2.62 micrograms.h/ml after the former and 10.95 +/- 2.65 micrograms.h/ml after the latter. The mean area under the concentration-time curve for primaquine was less than 0.1 micrograms.h/ml after either route of administration.

Animals↗
PubMed1993

Erysipelothrix tonsillarum isolated from dogs with endocarditis in Belgium.

Five strains of Erysipelothrix tonsillarum were isolated from dogs with endocarditis in Belgium. The identity and validity of the species was proved by serotyping, and biochemical and pathogenicity tests. All the isolates belonged to serovar 7 (E tonsillarum serovars); they produced acid from saccharose but did not induce any clinical sign of erysipelas in swine. These results suggest that some strains of E tonsillarum are a canine pathogen.

Animals↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗