[Case of renal hypouricemia causing exercise-induced acute renal failure].
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Acute Kidney Injury↗
Biomedical subjects
H Kubo
Publications and source records attributed to H Kubo.
DNA cleavage and 8-hydroxydeoxyguanosine formation caused by tamoxifen derivatives in vitro.
DNA damage caused by tamoxifen and its derivatives was examined by estimating the conversion of supercoiled pUC18 plasmid DNA to linear form by means of agarose gel electrophoresis. N-Desmethyltamoxifen induced DNA cleavage and its effect was enhanced by the addition of reducing agents such as dithiothreitol, NADPH and 2-mercaptoethanol. 4-Hydroxytamoxifen itself had little effect, but the cleavage was slightly enhanced by the addition of reducing agents. DNA damage was higher with alpha-hydroxytoremifene than with alpha-hydroxytamoxifen, which had a prominent effect only at high concentration. The cleavage by alpha-hydroxy derivatives were not enhanced by reducing agents. No damage was induced by tamoxifen, toremifene, 3-hydroxytamoxifen or N-desmethyltoremifene. The DNA cleavage by N-desmethyltamoxifen was inhibited by the addition of EDTA, mannitol, sodium azide, methionine, catalase and superoxide dismutase. The formation of 8-hydroxy-2'-deoxyguanosine was also examined with calf thymus DNA in vitro. A slight increase of its level was found with 4-hydroxytamoxifen in the presence of dithiothreitol and also with N-desmethyltamoxifen in the presence of NADPH, but alpha-hydroxytoremifene and alpha-hydroxytamoxifen were ineffective. These experimental data suggest that among metabolites of tamoxifen, N-desmethyltamoxifen and probably also 4-hydroxytamoxifen cause oxidative DNA damage in which redox cycling is involved. The DNA damage by alpha-hydroxytoremifene appears to involve a different mechanism from that by N-desmethyltamoxifen. Tamoxifen and toremifene are possibly metabolized to the forms contributing to DNA damage.
8-Hydroxy-2'-Deoxyguanosine↗
Residue 116 determines the C-terminal anchor residue of HLA-B*3501 and -B*5101 binding peptides but does not explain the general affinity difference.
HLA-B*3501 and -B*5101 molecules, which belong to the HLA-B5 cross-reactive group, bind peptides carrying similar anchor residues at P2 and the C-terminus, but differences are observed in the preference for a Tyr residue at the C-terminus and the affinity of peptides. A recent study of HLA-B*3501 crystal structure suggested that residue 116 on the floor of the F-pocket determines a preference for anchor residues at the C-terminus. In order to evaluate the role of the residue 116 in the peptide binding to both HLA-B*3501 and HLA-B*5101 molecules, we generated HLA-B*3501 mutant molecules carrying Tyr at residue 116 (B*3501-116Y) and tested the binding of a panel of nonamer peptides to the B*3501-116Y molecules by a stabilization assay with RMA-S transfectants expressing the mutant molecules. The substitution of Tyr for Ser at residue 116 markedly reduced the affinity of nonamer peptides carrying Tyr at P9, while it enhanced that of nonamer peptides carrying Ile and Leu at P9. On the other hand, the affinity of peptides carrying aliphatic hydrophobic residues at P9 to B*3501-116Y molecules was much higher than that to HLA-B*3501 and HLA-B*5101 molecules. These results indicate that residue 116 is critical for the structural difference of the F-pocket between HLA-B*3501 and HLA-B*5101 which determines the C-terminal anchor residues, while leaving other residues which differ between HLA-B*3501 and HLA-B*5101 may be responsible for the low peptide binding property of the latter.
Binding Sites↗
Onset age-dependent variations of three islet specific autoantibodies in Japanese IDDM patients.
The age related incidence rate of insulin-dependent diabetes mellitus shows a bimodal distribution, not only in Caucasians but also in Japanese. To evaluate the onset age-related autoimmune profile at presentation in insulin-dependent diabetes mellitus (IDDM), glutamic acid decarboxylase (GAD) autoantibody, islet cell antibody (ICA), and insulin autoantibody (IAA) were measured in 137 newly diagnosed Japanese IDDM patients with onset ages between 0-29 years. The prevalence of GAD autoantibody was significantly increased from the lowest (32%) in the 0-5 years onset age group to 75% in the 13-19 years onset age group (P < 0.05), whereas the IAA prevalence significantly decreased from the peak (48%) in the 6-12 years onset age group to 10% in the 20-29 years onset age group (P < 0.05). The ICA prevalence was increased from the lowest (32%) in the 0-5 years onset age group to the highest (53%) in the 20-29 years onset age group similar to that for the GAD autoantibody. Such results demonstrate that there was age-related autoimmune characteristics at presentation of IDDM in Japanese as well as in Caucasians.
Adolescent↗
Roles of histamine receptor in a guinea pig asthma model.
Histamine plays an important role in bronchoconstriction mediated by histamine receptors which provoke bronchial asthma attack. In this study, we measured H1 and H2 receptors in the guinea pig lung membrane fraction and obtained the following results. The maximum binding (Bmax) of H1 receptors in the guinea pig lung membrane fraction was significantly higher in the OA-sensitized group than that in the non-sensitized group, but affinity (Kd) did not differ between the groups. Otherwise, the maximum binding (Bmax) of H2 receptors in the guinea pig lung membrane fraction was significantly lower in the OA-sensitized group than that in the non-sensitized group. But affinity (Kd) did not differ between the groups. These findings suggest a close association of Histamine receptors both H1 and H2 in the pathology of asthma.
Animals↗
Effect of TYB-2285 on early and late bronchial responses and airway hyperreactivity in actively sensitized guinea pigs.
1. The effect of a new antiasthmatic drug, TYB-2285 [3,5-bis (acetoxyacetylamino)-4-chlorobenzonitrile], on dual bronchoconstriction and airway hyperreactivity in actively sensitized guinea pigs was investigated. 2. Immediate and late bronchial responses were induced at 1-10 min and 4-7 hr after antigen inhalation, respectively. Guinea pigs were pretreated with TYB-2285 (300 mg kg(-1) PO, as a single dose or consecutively for 7 days). 3. The immediate bronchial response was inhibited only by a multiple administration of TYB-2285. Late bronchial response was inhibited by both administration methods. 4. The numbers of eosinophils, neutrophils and macrophages, but not lymphocytes, in the bronchoalveolar lavage fluid were increased at 4 hr after antigen inhalation. TYB-2285, given singly and consecutively, decreased the numbers of total cells, eosinophils, neutrophils and macrophages. 5. Sensitized guinea pigs showed significant airway hyperreactivity to inhaled histamine. This airway hyperresponsiveness was reversed by a single administration of TYB-2285. 6. Luminol-dependent chemiluminescence of airway-infiltrated cells was slightly inhibited by TYB-2285 (20 microg ml(-1)). 7. The present study shows that TYB-2285 inhibits late asthmatic response and airway hyperresponsiveness, presumably by inhibiting the accumulation and activation of eosinophils and other inflammatory cells.
Animals↗
Effects of theophylline on lymphocyte phosphodiesterase activity.
1. To clarify part of the bronchodilating effects of theophylline, lymphocyte cyclic AMP (cAMP) and phosphodiesterase (PDE) activity in asthmatic patients and healthy adults were measured. 2. No clear differences in lymphocyte PDE activity were found regarding sexes, ages or the types of asthma. 3. Lymphocyte PDE activity in the asthma group was significantly higher than that in the control group. 4. Lymphocyte cAMP significantly increased at 30 and 60 min after intravenous injection of aminophylline in the asthma group. 5. Lymphocyte PDE activity significantly decreased 60 min after intravenous injection of aminophylline in the asthma group.
3',5'-Cyclic-AMP Phosphodiesterases↗
Role of GABA receptors in the bronchial response: studies in sensitized guinea-pigs.
BACKGROUND: Gamma-aminobutyric acid (GABA), an important inhibitory neurotransmitter in the mammalian central nervous system, is also found in peripheral tissues, including the lung. GABA has recently been shown to modulate the contraction of airway smooth muscle. OBJECTIVE: We studied the effect of GABA on the contractile properties of tracheal smooth muscle by measuring the tension of the trachea isolated from non-sensitized and ovalbumin (OA)-sensitized guinea-pigs under isometric conditions. METHODS: Guinea-pigs were sensitized by intraperitoneal doses of OA to prepare a bronchial asthma model. Tracheal spiral rings were prepared from the OA-sensitized as well as normal, non-sensitized guinea-pigs. Using the tracheal preparations, the effects of GABA and GABAa and GABAb receptor agonists (muscimol and baclofen) and antagonists (bicuculline and saclofen) on the basal tone of the trachea and on tracheal contraction induced by electrical field stimulation (EFS) were determined. The effect of GABA on tracheal contraction induced by exogenous acetylcholine was also studied. RESULTS: GABA and GABA agonists and antagonists had no effect on the basal tone of normal guinea-pig tracheae. Both GABAa and GABAb receptor agonists, as well as GABA, suppressed EFS-induced contraction of normal guinea-pig tracheae in a reversible, dose-dependent manner. Moreover, this suppression was reserved to the control level by either GABAa and GABAb receptor antagonists. In tracheal spiral ring prepared from OA-sensitized guinea-pigs, GABA and baclofen caused a smaller reversible inhibition of EFS-induced contraction than in normal tracheal spiral ring, while muscimol inhibited EFS-induced tracheal contraction to a similar extent to that observed in normal tracheae. GABA had no effect on the tracheal contractile response to acetylcholine. CONCLUSION: The results suggest that there may be a biological mechanism mediated by prejunctional GABAb receptors which attenuates cholinergic contraction of airway smooth muscle and that dysfunction of the receptors may underlie the airway obstruction in asthmatics.
Acetylcholine↗
Isolation and characterization of a unique sulfated ganglioside, sulfated GM1a, from rat kidney.
A novel class of sulfoglycosphingolipid, a sulfate analog of ganglioside, was isolated from mammals for the first time. This sulfated ganglioside was purified from rat kidney by column chromatographies on anion exchangers and silica beads. One-dimensional 1H NMR, compositional and permethylation analyses showed that this glycolipid has a Gg4Cer core with 1 mol each of sulfate ester and N- glycolylneuraminic acid (NeuGc) at C-3 of galactose. The major ceramide consisted of nonhydroxy fatty acids (24:0 and 22:0) and 4-hydroxysphinganine (t18:0), deduced from the compositional analysis and negative liquid secondary ion mass spectrometry (LSIMS). Mild acid hydrolysis and solvolysis produced compounds which correspond to Gg4Cer IV3-sulfate (SM1b) and II3NeuGcalpha-Gg4Cer (GM1a (NeuGc)), respectively. The abundant ions characteristic for sulfated mono- and disaccharides in high-energy collision-induced dissociation (CID) spectra were consistent with the structure at the non-reducing terminus, HSO3 -O- Hex -O- HexNAc- rather than the alternative structure, NeuGc -O- Hex -O- HexNAc-. The two-dimensional 1H NMR further evidenced the presence of a 3 -O- sulfated galactose in the molecule. From these results the complete structure was proposed to be HSO3-3Galbeta-3GalNAcbeta-4(NeuGcalpha-3)Galb eta-4Glcbeta-1Cer (II3NeuGcalpha-Gg4Cer IV3-sulfate).
Animals↗
Endosonographic probe-guided endoscopic resection of focal lymphoid hyperplasia of the rectum.
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Aged↗
Herpes simplex virus hepatitis in macrophage-depleted mice: the role of massive, apoptotic cell death in pathogenesis.
Infection with herpes simplex virus or hepatitis viruses can lead to fulminant hepatitis, but there is controversy about the underlying conditions needed for such disease. To investigate how the impairment of host defences might be involved, macrophages were depleted by administration of silica to mice before intravenous injection with herpes simplex virus type 1 (HSV-1). Such mice died rapidly and their livers were yellowish and shrunken (acute yellow atrophy), and occasionally grossly haemorrhagic. Small foci of apoptotic cells developed in the liver lobules; these rapidly became confluent and zonal over time. The overall lesion pattern was similar to massive hepatic necrosis, and there was extensive HSV replication in the liver lesions. In the liver, DNA fragmentation characteristic of apoptosis followed the time course of HSV-1 propagation. These findings suggest that one of the underlying conditions for fulminant viral hepatitis may be inadequate macrophage response, and that the massive hepatic damage, often defined as cell necrosis, may actually be apoptosis of liver cells subsequent to virus infection.
Alanine Transaminase↗
Treatment of insomnia by concomitant therapy with Zopiclone and Aniracetam in patients with cerebral infarction, cerebroatrophy, Alzheimer's disease and Parkinson's disease.
For insomniac patients, sleeping drugs are used: in addition, concomitant therapy with other drugs has been tried in an effort to prevent a decrease in the effects due to long-term continuous use. This report presents the results of a study on the sleeping effects in nine aged patients with insomnia associated with cerebrovascular and noncerebrovascular disorders who received concomitant therapy with Zopiclone and Aniracetam. The treatment in 7/9 cases (78%) was found to be effective, showing more than 50% prolongation of sleeping time, and in two cases (22%) was found to be ineffective. We discuss the mechanism of action referring to the literature.
Aged↗
Effects of thiopental on contractile and electrophysiological properties of single canine left ventricular cells.
The effects of thiopental on contraction, membrane potential and membrane ionic currents were studied in single canine left ventricular cells. Thiopental 10(-5) and 10(-4) mol/l reduced the cell-shortening from 7.02 +/- 0.64 microns to 5.66 +/- 1.39 and 3.48 +/- 0.64 microns respectively (mean +/- S.D., N = 10, 0.5 Hz). This effect was enhanced in higher (> 1.0 Hz) electrical stimulation frequencies. Also, thiopental decreased the plateau phase and shortened the duration of action potential. On the other hand, voltage clamp experiment revealed that thiopental 10(-6), 10(-5), and 10(-4) mol/l reduced peak Ca2+ current from 520 +/- 48 pA to 387 +/- 60 pA, 261 +/- 84 pA, and 84 +/- 36 pA respectively (mean +/- S.D., N = 8), and showed a use-dependent block of Ca2+ current. However, only a high dose of thiopental (10(-4) mol/l) inhibited the Na+ current. We conclude that the negative inotropic effect of thiopental on the heart is mediated mainly via inhibition of the Ca2+ current.
Animals↗
Theophylline suppresses the release of interleukin-4 by peripheral blood mononuclear cells.
To elucidate the mechanism of the anti-inflammatory effect of theophylline, peripheral blood mononuclear cells (PBMCs) collected from patients with bronchial asthma who had a RAST score for Dermatophagoides farinae (Df) > = 3 were stimulated with Df antigen, and the interleukin-4 (IL-4) production by the stimulated PBMCs was determined in the presence and absence of theophylline. The stimulated IL-4 production in the PBMCs was significantly suppressed by simultaneous treatment with theophylline (8 microg/ml). Furthermore, the intracellular 3',5'-adenosine monophosphate (cAMP) level following stimulation with Df was significantly higher in PBMCs simultaneously treated with theophylline (8 microg/ml) than in nontreated controls. These results suggest that theophylline suppresses the IL-4 production in inflammatory cells by increasing the intracellular cAMP level; this effect may thus provide an additional basis for the benefit of theophylline in antiasthmatic therapy.
Adult↗
Expression of RANTES by normal airway epithelial cells after influenza virus A infection.
The chemokine regulated on activation, normal T cells expressed and secreted (RANTES), is a C-C chemokine and a potent chemoattractant for monocytes, T lymphocytes, basophils, and eosinophils. Its expression by human airway epithelium has been demonstrated both in vitro and in vivo. We investigated whether RANTES is expressed by normal human airway epithelial cells after influenza viral infection and examined its bioactivity. Epithelial cells were obtained from bronchial tissue or nasal polyps of patients who had undergone lobectomy for lung cancer or polypectomy for nasal polyps. These cells were cultured by the outgrowth method. Cultured cells were infected with influenza virus A (subtype H3N2) after which the supernatants and the cells were collected 8 to 72 h after infection. RANTES mRNA (messenger RNA) was analyzed by the reverse transcriptase-polymerase chain reaction and Southern blot analysis of its product. Concentrations of RANTES in the supernatants were analyzed by enzyme-linked immunosorbent assay. RANTES protein and mRNA were not detected in the media of uninfected cells. PCR products for RANTES were clearly detected in nasal and bronchial epithelial cells 24 h after infection. Southern blot analysis confirmed that the PCR products were indeed specific for RANTES mRNA. Twenty-four to 72 h after infection, significant levels of RANTES protein were detected in culture media. We also investigated the chemotactic activity of the supernatant of cultured cells. The supernatant of the cells 48 h after infection had potent chemotactic activity for eosinophils, which was attenuated by the addition of anti-RANTES antibodies. These findings suggest that influenza virus infection may induce expression of bioactive RANTES by normal human bronchial and nasal epithelial cells.
Bronchi↗
Automatic system for the assay of guanidino compounds to assess uremic status and effect of hemodialysis.
An automated HPLC system coupled with fluorometry was established for the sensitive, rapid, and accurate assay of serum guanidines. Naturally fluorescent materials characteristic of the sera of uremic patients (uremic fluorescences) which interfere with the assay were removed simultaneously with deproteinization. Application of this method revealed that the uremic patients who are capable of excreting urine under hemodialysis therapy show low serum guanidinosuccinic acid levels. The interval between hemodialysis sessions in one of these patients was prolonged while monitoring guanidinosuccinic acid level using the present method without any hazardous effect.
Autoanalysis↗
Synthesis and antihypertensive activity of 4-(diazabicyclo[4.1.0]-heptenyloxy)benzopyran derivatives and their analogues.
A series of 3,4-dihydro-3-hydroxy-4-[(5-oxo-3,4-diazabicyclo[4.1.0]hept- 2-en-2-yl)oxy]-2H-1-benzopyrans and their analogues were synthesized and evaluated on potassium channel opening and hypotensive activities. Compound (-)-13B with a (4-methyl-5-oxo-3,4-diazabicyclo[4.1.0]hept-2-en-2-yl)oxy group for the 4-position of the benzopyran ring was 3 times as potent as EMD 57283 (II), the lead compound, in hypotensive activity. The results would demonstrate that 5-oxo-3,4-diazabicyclo[4.1.0]hept-2-en-2-yloxy moieties are effective as the substituents at the 4-position of benzopyran-type potassium channel openers.
Animals↗
Pineal dermoid cyst developing 18 years after gross total removal of a pineal mature teratoma.
A 21-year-old male presented with a pineal dermoid cyst manifesting as headache and diplopia. He had undergone gross total removal of a pineal mature teratoma 18 years before and had done well until recently. Diffusion-weighted magnetic resonance imaging showed a region of high signal intensity due to a round mass in the pineal region and extending into the trigone of the right lateral ventricle. Subtotal excision of the tumor was achieved. Histological examination showed an epidermoid cyst consisting of keratinized stratified squamous epithelium and connective tissue. Intraoperative observation had detected black hairs, so the diagnosis was dermoid cyst. The dermoid cyst may have arisen from a microscopic remnant of the cyst wall of the original pineal mature teratoma. The regrowth of a dermoid cyst 18 years after gross total removal of a mature cystic teratoma in the pineal region is exceptional. However, careful follow-up of patients who undergo gross total removal of a pineal teratoma is recommended for a period more than that of the patient's age at surgery plus 9 months.
Adolescent↗