A solitary hematogenous metastasis to the gastric wall from renal cell carcinoma four years after radical nephrectomy.
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Carcinoma, Renal Cell↗
Biomedical subjects
A Ohara
Publications and source records attributed to A Ohara.
Recovery of flagellar inner-arm dynein and the fertilization tubule in Chlamydomonas ida5 mutant by transformation with actin genes.
The ida5 mutant of Chlamydomonas, first isolated as a mutant lacking a subset of axonemal inner-arm dyneins, has recently been shown to lack conventional actin owing to a serious mutation in its gene. It lacks inner-arm dyneins probably because actin is an essential subunit for their assembly. In addition, male gametes of ida5 are unable to produce the fertilization tubule, a structure that contains a core of actin filament bundles. To establish that those observed deficiencies are solely attributable to the loss of actin, and to provide a basis for future studies on the actin function in this organism, we examined in this study whether transformation of this mutant with cloned actin genes can rescue the mutant phenotypes. Cotransformation of the double mutant ida5arg2 with the wild-type actin gene and arginino-succinate lyase gene that suppresses the arg2 mutation yielded several transformants that displayed increased motility. All of them were found to have acquired the introduced actin gene in the genome and the product actin in the flagella, and regained the missing inner-arm dyneins and wild-type motility. In addition, most transformants also became able to grow the fertilization tubule when mating reaction was induced. In addition to the wild-type actin gene, we also used a chimeric actin gene in which the N-terminal 12 amino-acid sequence of Chlamydomonas actin was replaced by that of the greatly divergent Tetrahymena actin. Transformants with this gene also resulted in recovery of inner-arm dynein and 70-80% of the wild-type level of motility. These results established that the lack of inner-arm dynein and the fertilization tubule in ida5 are consequences of its loss of conventional actin. Furthermore, they demonstrate that Chlamydomonas offers an excellent experimental system with which to study the structure-function relationship of actin by means of mutant analysis.
Actins↗
Myelodysplastic syndrome and acute myelogenous leukemia as a late clonal complication in children with acquired aplastic anemia.
The improved outcome of acquired aplastic anemia (AA) has revealed later complications, such as myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). We retrospectively analyzed 167 children with severe acquired AA. Eleven of 50 children treated with cyclosporin (CSA) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) developed MDS/AML; 8 of these were within 36 months of the diagnosis of AA, much earlier than previous reports. Six of the 11 children received rhG-CSF exceeding 10 microg/kg/d, and 9 received rhG-CSF therapy for over 1 year. Ten children showed monosomy 7 at diagnosis of MDS. All of the 11 children were administered both CSA and rhG-CSF. There was no development of MDS/AML among 41 children treated with either CSA or rhG-CSF or among 48 children who underwent bone marrow transplantation. A well-controlled clinical trial is warranted to determine whether therapeutic modalities affect the development of MDS/AML in children with severe acquired AA.
Acute Disease↗
Laser Doppler skin blood flow and sympathetic nervous responses to surgical incision during halothane and isoflurane anesthesia.
The aim of the present study was to evaluate whether a sudden decrease in skin blood flow measured using a laser Doppler velocimeter reflects sympathetic nervous response to surgical skin incision during halothane (n = 17) and isoflurane (n = 16) anesthesia in 33 ASA physical status I or II patients scheduled for laparotomy. Plasma norepinephrine concentrations in the responding patients who showed a sudden decrease in the skin blood flow after surgical incision increased significantly and continued to increase 1-10 min after skin incision under halothane and isoflurane anesthesia. Although plasma norepinephrine concentrations in the nonresponders did not increase after surgical incision with halothane, the concentrations increased significantly at 1 min, but not at 3 and 10 min, after skin incision with isoflurane. The results indicate that the sudden decrease in laser Doppler flow reflects the sympathetic response to surgical incision. However, these also suggest that the factors that control the skin blood flow may not be simply sympathetic but may reflect other modulators as well. Plasma epinephrine concentration increased during skin incision, but the concentrations did not differ between the patients with and without a sudden decrease in skin blood flow. Increases in systolic blood pressure and rate-pressure product on skin incision were also significantly more in patients with skin blood flow response compared with those without the response. The magnitude of changes in plasma norepinephrine concentration and hemodynamic variables with skin incision was greater with isoflurane than with halothane at the same minimum alveolar anesthetic concentration level.
Adult↗
A comparative study of the antinociceptive action of xenon and nitrous oxide in rats.
UNLABELLED: We attempted to clarify the mechanism of antinociceptive action induced by xenon and nitrous oxide. Eighty percent of nitrous oxide or 80% xenon was applied to rats inside enclosed clear plastic glass cylinders with their tails protruding for assessment of the tail-flick response to radiant heat. With repeated testing, there was a rapid reduction to nitrous oxide antinociception within 90 min, which was interpreted as development of tolerance, but not to xenon antinociception. Nitrous oxide antinociception was blocked by the intraperitoneal administration of 0.1 or 1.0 mg/kg yohimbine, but not by 1.0 or 5.0 mg/kg L659-066 or by 5.0 or 10 mg/kg naloxone. Xenon antinociception was not affected by any of these drugs. Yohimbine and L659-066 are characterized as alpha 2-adrenoceptor antagonists. Although yohimbine penetrates the blood-brain barrier after systemic administration, L659-066 does not penetrate it and act peripherally. Therefore, the results indicate that alpha 2-adrenoceptors, but not opioid receptors, may play a key role in antinociception induced by nitrous oxide in the central nervous system. Furthermore, the mechanism of xenon antinociception differs from that of nitrous oxide because it does not involve either alpha 2 or opioid receptors. IMPLICATIONS: The precise mechanism of antinociceptive action of nitrous oxide and xenon remains unknown. It is still controversial whether an opioid system plays a role in antinociception induced by nitrous oxide. The results of the study showed that antagonism of central alpha 2-adrenoceptors, but not opioid receptors, reverses the antinociception induced by nitrous oxide but not by xenon, which indicates that alpha 2-adrenoceptors may play a key role in nitrous oxide antinociception.
Analgesics, Non-Narcotic↗
Cardiovascular effects of an ultra-short-acting nitric oxide-releasing compound, zwitterionic diamine/NO adduct, in dogs.
BACKGROUND: This study was conducted to clarify the cardiovascular effects of a new NO-releasing compound, NOC-7, and to compare it with other nitrovasodilators, sodium nitroprusside (SNP) and nitroglycerin, in dogs anesthetized with pentobarbital. METHODS AND RESULTS: A bolus injection of NOC-7 decreased mean aortic blood pressure in a dose-dependent manner. The onset was rapid and the recovery quick. Continuous infusion of NOC-7 decreased mean aortic pressure from 115 +/- 3.9 to 84 +/- 2.9 mm Hg and infusion of SNP, from 118 +/- 3.8 to 87 +/- 3.1 mm Hg. The optimum doses of NOC-7 and SNP were determined to be 2.73 +/- 0.77 and 11.5 +/- 6.1 micrograms.kg-1.min-1, respectively. During infusion of NOC-7, heart rate and cardiac output were increased (P < .05), pulmonary artery pressure was not changed, and systemic and pulmonary vascular resistances were decreased (P < .05). Electromagnetic flowmetry showed that portal venous and internal carotid arterial blood flow were increased (P < .05) and that hepatic and renal arterial blood flows were not changed. These hemodynamic changes during NOC-7 infusion were similar to those with SNP. The plasma level of NO2-/NO3 did not change, but methemoglobin increased slightly (P < .05). Comparison between hypotensive responses before and after a 3.5-hour infusion of NOC-7 or nitroglycerin showed that acute tolerance developed to nitroglycerin but not to NOC-7. CONCLUSIONS: The results indicate that NOC-7 may be useful as an ultra-short-acting nitrovasodilator that has no major adverse effect or tolerance.
Animals↗
A new nitric oxide donor, NOC-18, exhibits a nociceptive effect in the rat formalin model.
The utility of a new nitric oxide (NO) donor, NOC-18, and the contribution of the neurotransmitter NO to nociception in response to tissue injury in rats, were examined following the subcutaneous injection of formalin into the hindpaw. This model induces biphasic responses in pain-related behavior, such that C-fiber activation during the first phase triggers a state of central sensitization characterized by the second phase. Formalin-induced nociceptive behavior was facilitated by intracerebroventricular administration of NOC-18 in the second phase, but not the first phase. This enhancement was completely abolished by the soluble guanylate cyclase inhibitor, methylene blue. These findings indicate that NO causes nociception via the NO-cGMP pathway in the central nervous system and NOC-18 proved to be a convenient and useful tool for the investigation of nociception-related NO.
Animals↗
Effects of FSH on serum immunoreactive inhibin levels in the luteal phase of the menstrual cycle.
OBJECTIVE: FSH causes a dose-related increase in circulating immunoreactive inhibin (INH) in the follicular phase of the menstrual cycle, while LH is the major stimulus to INH secretion by the corpus luteum. The present study was undertaken to assess whether FSH can also stimulate INH production during the luteal phase. DESIGN: Normal volunteers were treated with a single injection of LH-free FSH (Metrodin, 150 units) or saline as control, during the early, mid- or late luteal phase of the cycle, with subsequent hormone measurements. PATIENTS: The 21 volunteers were aged 19-29. Seven subjects given FSH and 8 controls were studied in the early luteal phase, 1-4 days post ovulation. Eight FSH treated subjects and 10 controls were studied in the midluteal phase, 5-9 days post ovulation, and 6 each, respectively, were studied in the late luteal phase. MEASUREMENTS: Oestradiol (E2), progesterone (P), and INH were measured by previously described radio-immunoassays. RESULTS: In both the early and mid-luteal phases, FSH caused a significant rise in INH (early, from 778 to 922 U/l, mid-luteal 1553 to 2090 U/l) and E2 (early 371 to 545 pmol/l, mid-luteal 528 to 636) while there was no significant change in P. No significant changes occurred in the saline treated subjects. In the late luteal phase FSH prevented the significant fall in INH seen in the controls, whilst there was no effect on E2 or P. CONCLUSIONS: It was concluded that both FSH and LH are capable of modulating inhibin production during the luteal phase of the menstrual cycle. FSH may exert its actions on the corpus luteum or alternatively on developing follicles. The present study cannot clearly distinguish between these possibilities.
Adult↗
Ketamine inhibits nitric oxide production in mouse-activated macrophage-like cells.
We have investigated the effects of ketamine on nitric oxide produced by activated macrophages using a murine macrophage-like cell line, J774. Cells were incubated for 18 h under stimulation with lipopolysaccharide and interferon-gamma or lipoteichoic acid and interferon-gamma, with various concentrations of ketamine (6-600 mumol litre-1). Nitric oxide production was assessed by measuring nitrite, a stable by-product of nitric oxide breakdown, in the medium. Other N-methyl-D-aspartate receptor antagonists, MK-801 (150 mumol litre-1) and dextromethorphan (150 mumol litre-1) were also tested. In addition, we studied the effects of ketamine on production of tumour necrosis factor-alpha by activated macrophages. Ketamine inhibited nitrite production dose-dependently with both lipopolysaccharide- and lipoteichoic acid-activated macrophages by up to approximately 65% at the highest ketamine concentration (600 mumol litre-1). Neither MK-801 nor dextromethorphan had an inhibitory effect. Ketamine also suppressed production of tumour necrosis factor-alpha. The data show that ketamine inhibited nitric oxide production by activated macrophages probably, in part, via inhibition of production of tumour necrosis factor-alpha, an autocrine stimulatory factor for nitric oxide production, but not via the NMDA receptor pathway, which is involved in neuronal nitric oxide production.
Anesthetics, Dissociative↗
Inhibitory effect of acetylshikonin on the activation of NADPH oxidase in polymorphonuclear leukocytes in both whole cell and cell-free systems.
The effects of acetylshikonin (AS) on the activation of NADPH oxidase (EC 1.6.99.6) in guinea pig polymorphonuclear leukocytes (PMNs) in both whole cell and cell-free activation systems were investigated. When PMNs were treated with AS before exposure to phorbol myristate acetate (PMA), superoxide (O2-) generation in these cells was significantly reduced, but after exposure of PMNs to PMA, inhibition of O2- generation by AS did not occur. Thiol compounds completely abolished the inhibitory effect of AS on the O2- generating activity of PMNs. In the cell-free system, AS inhibited the activation of NADPH oxidase induced by myristate in a combination of cytosol and membrane fractions obtained from intact PMNs, but did not inhibit the activity of NADPH oxidase already induced. These results suggest that AS inhibits the generation of NADPH oxidase complex in the activation of respiratory burst of PMNs, but does not directly inhibit the activity of NADPH oxidase already generated.
Animals↗
NOC, a nitric-oxide-releasing compound, induces dose dependent apoptosis in macrophages.
The ability of exogenous nitric oxide (NO) to induce apoptosis in macrophages was analyzed using NOC, a NO-releasing compound, as a source of NO. Exogenous NO was shown to induce apoptosis in a dose dependent manner. Quantitative analysis revealed that the amount of NO required to induce apoptosis in more than half of macrophages exposed was 100 times larger than that for endogenous NO-induced apoptosis. NOC proved to be a convenient and useful tool for investigation of apoptosis related to NO.
Animals↗
Primary structure of a coagulant enzyme, bilineobin, from Agkistrodon bilineatus venom.
The amino acid sequence and disulfide bridge location of the coagulant enzyme, named bilineobin, isolated from the venom of Agkistrodon bilineatus was determined by Edman sequencing of the peptides derived from digests with cyanogen bromide, clostripain, Staphylococcus aureus V8 protease, trypsin, and chymotrypsin. This enzyme has a molecular weight of 57,000 Da by sodium dodecyl sulfate-polyacrylamide gel electrophoresis; however, bilineobin consists of 235 amino acids and has a calculated molecular weight of 26,481. The enzyme contains fucose, GlcNAc, galactose, mannose and NeuAc and six N-linked glycosylation consensus sites. The carboxyterminal amino acid, proline, was determined using carboxypeptidase Y. The six disulfide bonds of bilineobin link Cys78 to Cys234, Cys120 to Cys188, Cys178 to Cys203, Cys7 to Cys141, Cys152 to Cys167, and Cys28 to Cys44. The amino acid sequence similarity to flavoxobin (T.C. Shieh et al., 1988, J. Biochem (Tokyo) 103, 596-605) and batroxobin (N. Itoh et al., 1987, J. Biol. Chem. 262, 3132-3135) was 67%. The deglycosylated enzyme more rapidly generated fibrinopeptide A than native bilineobin.
Agkistrodon↗
Intracerebroventricular administration of a nitric oxide-releasing compound, NOC-18, produces thermal hyperalgesia in rats.
This study was undertaken to define the role of nitric oxide (NO) in central nociceptive mechanisms by intracerebroventricular injection of an NO-releasing compound, NOC-18, in rats. The nociceptive threshold was evaluated by the radiant heat tail-flick test. Sixty-nine rats were divided into the seven groups, and the following drugs were injected intracerebroventricularly in 5 microliters of saline: no drug (control) (n = 13), 15 micrograms of NOC-18 (n = 15); 150 micrograms of NOC-18 (n = 9); 100 micrograms of N-nitro-L-arginine methyl ester (L-NAME) (n = 8); 15 micrograms of NOC-18 + 100 micrograms of L-NAME (n = 8); 10 micrograms of methylene blue (MB) (n = 8); 15 micrograms of NOC-18 + 10 micrograms of MB (n = 8). NOC-18 caused a dose-dependent curtailment (7% and 23% decreases for 15 micrograms and 150 micrograms of NOC-18, respectively) of the tail-flick latency during the period from 15 to 120 min. L-NAME caused prolongation (15% maximum) of the tail-flick latency during the period from 15 to 150 min. However, NOC-18-induced hyperalgesia was not influenced by L-NAME. MB also caused prolongation (9% maximum) of the tail-flick latency during the period from 15 to 150 min, and completely blocked the hyperalgesia induced by 15 micrograms of NOC-18. These findings indicate that the NO-cGMP pathway is directly involved in thermal hyperalgesia in the brain.
Animals↗
Pulmonary resistance in dogs: a comparison of xenon with nitrous oxide.
Xenon (Xe) may cause an increase in airway resistance due to its high density and viscosity. The object of this study was to examine the effects of Xe on pulmonary resistance using dog models with normal and methacholine-treated airways. During anaesthesia 22 mongrel dogs' tracheas were intubated and the lungs were mechanically ventilated with 70% N2/30% O2 as a control gas. The gases 70% nitrous oxide (N2O), 50% N2O, 70% Xe and 50% Xe were administered in a random order for 25 min. Bronchoconstriction was produced by a continuous infusion of methacholine, 0.22 mg.kg-1.hr-1. Pulmonary resistance (RL) was calculated by the isovolume method using flow at the airway opening, volume and transpulmonary pressure. In normal dogs, RL breathing 70% Xe (mean +/- SEM, 0.84 +/- 0.12 cm H2O.L-1.sec-1) was greater (P < 0.05) than with 70% N2O, 50% N2O or control gas (0.61 +/- 0.08, 0.59 +/- 0.06 and 0.62 +/- 0.06 cmH2O.L-1.sec-1). Breathing 50% Xe the RL (0.77 +/- 0.10 cmH2O.L-1.sec-1) was not different from 50% N2O or control. Methacholine infusion increased RL 3.92 +/- 1.98 (mean +/- SD) times. The RL breathing 50% Xe (2.55 +/- 0.44 cmH2O.L-1.sec-1) was not greater than during 50% N2O or control (2.08 +/- 0.33 and 2.13 +/- 0.33 cmH2O.L-1.sec-1) in methacholine-treated dogs. The data suggest that inhalation of high concentrations of Xe increases airway resistance, but only to a modest extent in dogs with normal or methacholine-treated airways.
Airway Resistance↗
Inactivation of cholinesterase by ascorbic acid in the presence of cupric ions: a possible mechanism for the inactivation of an enzyme by the metal-catalyzed oxidation system.
The mechanism of inactivation of cholinesterase (EC 3.1.1.8) by the Cu2+ -ascorbic acid (AsA) system was investigated. Incubation of the enzyme with the Cu2+ -AsA system under aerobic conditions resulted in an irreversible loss of enzyme activity. At low concentrations of Cu2+, the extent of inactivation showed the same dependence in accordance with the extent of oxidation of AsA. Saturation kinetics were observed with respect to the concentration of AsA. No change in the dissociation constant of the enzyme-AsA complex was observed at various concentrations of Cu2+. Catalase at a low concentration partially protected the enzyme from the inactivation, but did not affect the oxidation of AsA. In addition, catalase at a high concentration completely protected both the enzyme from inactivation and the AsA from oxidation. Both thiourea and thiocyanate completely protected the enzyme from the inactivation, while AsA was partially oxidized only in the initial phase. Our proposed mechanism for the inactivation of an enzyme by the Cu2+ -AsA system is as follows. A ternary complex involving the enzyme, Cu2+ and AsA is formed. This is followed by a redox reaction within the complex which generates a superoxide (.O2-) and hydrogen peroxide (H2O2). The H2O2 then reacts with .O2- in a Haber-Weiss reaction producing the hydroxyl radical (.OH). Another role of H2O2 is the conversion of the reduced Cu+ within the complex to Cu2+. Thus, repeated cycles of the redox reaction between the Cu2+ and AsA take place at the same locus, producing multiple .OH, which causes its complete inactivation.
Animals↗
Nonenzymatic glycation of transferrin: decrease of iron-binding capacity and increase of oxygen radical production.
The total iron-binding capacity (TIBC) and iron contents of diabetic rat serum, as well as the iron-binding capacity of glycated transferrin and oxygen radical production by the glycated proteins were examined. The TIBC and iron content of diabetic rat sera were found to be much lower than those of control rat sera. Incubation of human serum with glucose in vitro resulted in a significant fall of its unsaturated iron-binding capacity (UIBC) with time. When apotransferrin was incubated with glucose, its UIBC significantly decreased. The iron content of holotransferrin was markedly reduced by incubation with bathophenanthroline sulphonic acid (BPSA) in the presence of glucose, although the content was not altered by incubation with BPSA alone. The generation of superoxide radical (O2-) and hydroxyl radical (OH.) by the glycated holotransferrin was much greater than that by glycated apotransferrin. Glycated holotransferrin showed significantly accelerated hydroxyl radical production by the hypoxanthine-xanthine oxidase system, while intact holotransferrin did not. Treatment of holotransferrin with glucose caused the fragmentation of the protein, while the same treatment of apotransferrin did not. These results suggest that iron ions in the glycated transferrin molecule are bound loosely to the protein and are redox-active and the glycated holotransferrin produces oxygen radicals including O2- and OH. efficiently, and that the glycated transferrin does not function as an iron-binding protein.
Animals↗
A case report of nephrotic syndrome associated with rifampicin therapy.
We describe nephrotic syndrome occurring in a 53-year-old male patient on continuous rifampicin (RFP) therapy for pulmonary tuberculosis. After the pulmonary tuberculosis was improved by chemotherapy that included RFP, administration of Isoniazid and RFP was continued. After 16 weeks, he suddenly developed nephrotic syndrome, but never developed acute renal failure. He was admitted to hospital and renal biopsy was performed revealing minor glomerular abnormalities and few interstitial changes in light microscopy. No positive immunofluorescent microscopic findings were obtained without fibrinogen. Thus, minimal change nephrotic syndrome (MCNS) was diagnosed. In contrast, electron microscopy showed several injurious glomerular changes, such as the elevation of the endothelial layer, local widening of the subendothelial space which was filled with fine granular or fibrillar materials, irregularity of the endothelial investment, swelling or shrinkage of the endothelial cells, compatible with those seen in many diseased conditions supposedly caused by clinical or subclinical localized intravascular coagulation. Discontinuation of RFP administration completely relieved the patient of MCNS with the aid of predonisolone therapy. Thus, this patient might not have been a case of incidental, but rather drug (RFP)-induced MCNS.
Humans↗
Characterization and amino-terminal sequence of phospholipase A2-II from the venom of Agkistrodon bilineatus (common cantil).
1. Phospholipase A2 was isolated from the venom of Agkistrodon bilineatus by Sephadex G-75 and CM-Cellulose column chromatographies. 2. The purified phospholipase A2 gave a single band on disc polyacrylamide gel electrophoresis, sodium dodecyl sulfate polyacrylamide gel electrophoresis and ODS-HPLC. 3. The enzyme preparation had a mol. wt of 14,000, isoelectric point of pH 10.12 and possessed 121 amino acid residues. 4. The enzyme hydrolyzed the phospholipids phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl inositol and phosphatidyl serine. 5. The contraction of mouse diaphragm was inhibited by phospholipase A2-II. 6. Phospholipase A2 activity of this preparation was inhibited by ethylenediamine tetraacetic acid, ethyleneglycol (beta-aminoethyl) N,N,N',N'-tetraacetic acid, p-bromophenacyl bromide or N-bromosuccinimide, but not by iodoacetic acid or diisopropyl fluorophosphate. 7. The amino-terminal sequence of the PLA2-II was determined.
Amino Acid Sequence↗