Leiomyomas of the lower extremity.
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Foot Diseases↗
Biomedical subjects
A Danon
Publications and source records attributed to A Danon.
Hyperthermal surface ionization of mercury from Pt(111).
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Journal Article↗
Fatty acid binding protein (FABP) modulates prostaglandin E binding to rat epididymal adipocyte membrane similarly to albumin.
Albumin enhances prostaglandin E2 (PGE2) binding to isolated epididymal adipocyte membrane and also binds PGE2 with low affinity. On the other hand, S-100, ovalbumin and albumin-stearate failed to bind PGE2, as shown by ultrafiltration, and also failed to enhance PGE2 binding to the isolated adipocyte membranes. These results suggested that albumin enhances PGE2 binding possibly by serving as a carrier for the prostaglandin molecules. 3 mM warfarin or 1 mM phenylbutazone inhibited PGE2 binding to albumin by 70% and 95%, respectively, but both drugs failed to affect the enhancement of PGE2 binding to the isolated adipocyte membrane in the presence of albumin. These results exclude the possibility that PGE2 bound to albumin is more accessible to the prostaglandin receptor than free PGE2 in solution. Finally it is shown that fatty acid binding protein (FABP), a cytosolic protein which binds specifically PGE1 but not PGE2, enhances PGE1 and PGE2 binding to isolated adipocyte membranes similarly to albumin. The physiological implications of these findings are discussed.
Adipose Tissue↗
Acetaminophen hepatotoxicity: is there a role for prostaglandin synthesis?
The hepatotoxicity of acetaminophen (APAP) overdose depends on metabolic activation to a toxic reactive metabolite via hepatic mixed function oxidase. In vitro studies have indicated that APAP may also be cooxidized by prostaglandin H synthetase. The present experiments were designed to assess the possible contribution of hepatic prostaglandin synthesis to APAP toxicity. Adult fed male mice were overdosed with 400 mg APAP/kg. Liver toxicity was estimated by measurement of serum transaminases. Hypertonic xylitol or sodium chloride (2250 mOsm/l), administered intragastrically to stimulate prostaglandin synthesis, increased APAP toxicity. By contrast, the cyclooxygenase inhibiting drugs aspirin (at 25 mg/kg) and indomethacin (at 10 mg/kg) protected against APAP-induced toxicity. APAP kinetics were not affected by hypertonic xylitol or indomethacin, nor were hepatic glutathione levels in overdosed mice. Imidazole, a nonspecific thromboxane synthetase inhibitor, also protected overdosed mice. This drug prolonged hexobarbital sleeping time and prevented the depletion of hepatic glutathione that followed APAP intoxication. Thus, the data support the conclusion that APAP-induced hepatoxicity may be modulated not only by inhibition of cytochrome P450 mediated oxidation, but also by controlling hepatic cyclooxygenase activity.
Acetaminophen↗
Role of inositol-1-phosphatase inhibition in the mechanism of action of lithium.
Li inhibition of noradrenergic adenylate cyclase may be due to inhibition by Li of agonist-induced increases in GTP binding to G-protein. Such inhibition by Li of G-protein function could have effects on phosphatidyl-inositol-mediated second messenger systems as well as on cyclic AMP-mediated systems. However, Sherman, Berridge and others have proposed that Li affects phosphatidylinositol metabolism by inhibiting inositol-1-phosphatase. We recently have been able to measure inositol-1-phosphatase in human red blood cells. Preliminary data on patients treated with Li compared with controls suggests that the enzyme is indeed inhibited in vivo in patients undergoing Li treatment. However, a series of experiments in rats on addition of inositol to Li treatment did not find that inositol could reverse Li effects. Chronic oral high dose inositol does not reverse Li-induced polyuria (measured by polydipsia), Li-induced weight loss or Li-induced depression of exploratory behavior. These results suggest that Li inhibition of inositol-1-phosphatase indeed occurs in vivo. However, the physiological significance of inositol-1-phosphatase inhibition is not yet established.
Animals↗
Extranodal head and neck sinus histiocytosis with massive lymphadenopathy.
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Adult↗
Serum amyloid A, an acute phase protein, inhibits platelet activation.
The effect of serum amyloid A, an acute phase protein, on platelet function was studied. Serum amyloid A was isolated and purified from sera of patients with recent trauma. Serum amyloid A inhibited thrombin-induced gel-filtered platelet aggregation. However, it did not inhibit aggregation induced by collagen or adenosine diphosphate, nor did it influence the aggregation of platelet-rich plasma activated with thrombin. Further studies of its effect on thrombin-induced activities showed that serum amyloid A, at concentrations of 25 to 100 micrograms/ml (which are found in mild acute events), suppressed the increase of cytosolic [Ca2+], thromboxane generation, and carbon 14-labeled serotonin release in a dose-dependent fashion. Serum amyloid A did not interfere with the clotting or amidolytic activities of thrombin. Therefore, the data suggest a protective role for serum amyloid A in thromboembolic disease by specific interaction with thrombin-induced platelet activation. Amyloid A protein also markedly inhibited thrombin-induced platelet aggregation. Because amyloid A is homologous to the N-terminal portion of serum amyloid A, the observed activity probably resides in that part of the molecule. This finding may be of importance in localization of the active site on serum amyloid A.
Acute-Phase Proteins↗
Asymptomatic or mildly symptomatic effort-induced myocardial ischemia: plasma beta-endorphin and effect of naloxone.
The hypothesis that endogenous opioids may be involved in reduced exercise-induced ischemic pain or in silent ischemia was tested. Fifteen male patients with coronary artery disease were tested in a randomized, double-blind crossover study. After a preliminary screening effort test they were divided into two groups: the first group of nine patients received an i.m. injection of naloxone 0.4 mg, or saline as placebo, and the second group, comprising six patients, received 4 mg naloxone or saline i.v. Effort testing was performed at weekly intervals on an ergometric bicycle, following the Bruce protocol. ECG, heart rate, blood pressure and pain perception were monitored continually. Blood was sampled through an indwelling venous catheter for beta-endorphin determination before, at the peak of, and 10-20 min following exercise. ST depression, heart rate, blood pressure and the double product were similar after naloxone and following saline administration. Beta-endorphin concentrations in plasma were significantly increased following exercise in the second group of patients. The increase in beta-endorphin concentration was larger when the patients were pretreated with naloxone (4 mg) than with placebo. However, chest pain was not significantly altered by either dose of naloxone.
Angina Pectoris↗
Cardiac glycoside toxicity in small laboratory animals.
Cardiac glycosides are frequently administered to laboratory animals for research purposes. The effects achieved depend not only upon the particular glycoside and dose administered, but also upon an entire array of variables from the species of animal to the temperature of the animal housing facility. We review a number of these factors and their influence upon the effects achieved by the administration of cardiac glycosides to laboratory animals.
Age Factors↗
Phosphate Starvation Inducible Metabolism in Lycopersicon esculentum: III. Changes in Protein Secretion under Nutrient Stress.
Phosphate starvation increased the secretion of at least six proteins by suspension cultured tomato (Lycopersicon esculentum L. and L. pennellii) cells. Cells exhibited a biphasic response to phosphate (Pi) starvation. The early phase involved enhanced secretion of three proteins in response to transfer to a Pi-depleted media, while biomass accumulation continued at the same rate as in the Pi-sufficient cells. Severe starvation, defined as inhibition of biomass accumulation, induced enhanced secretion of three additional proteins. After sodium dodecyl sulfate-polyacrylamide gel electrophoresis, media proteins were immunoblotted with antibodies reacting specifically to oligosaccharides processed by the Golgi apparatus. Binding patterns showed that the enhancement in secretion during both phases of starvation was Golgi-mediated. Cells undergoing severe starvation had a respiration rate approximately twice that of unstressed cells and secreted 4.4 times more protein into the media per unit biomass. These data suggest overlapping Pi starvation-specific and global stress responses in plant cells. Under these conditions, Golgi-mediated protein secretion is enhanced. We present evidence for phosphate starvation inducible enhancement of Pi uptake. Secreted proteins specific for N and Fe starvation are also identified.
Journal Article↗
Surface-molecule electron transfer: I2-diamond scattering at 1-12 eV.
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Journal Article↗
Lithium inhibits adrenergic and cholinergic increases in GTP binding in rat cortex.
Lithium is a unique drug with therapeutic as well as prophylactic value for both manic and depressive phases of manic-depressive illness. The precise mechanisms of its clinical efficacy remain unknown, but there are two main theories of its biochemical action. One proposes that lithium inhibits adrenergically activated adenylate cyclase function whereas the other suggests that it inhibits phosphatidyl inositol turnover, which is known to be activated by cholinergic agonists. Neither mechanism alone, however, can explain both the antimanic and antidepressant effects of lithium. Because of the pivotal role of G proteins in post-receptor information transduction, we have investigated the interaction of lithium with G protein function. Lithium at therapeutically efficacious concentrations completely blocked both adrenergic and cholinergic agonist-induced increases in [3H]GTP binding to membranes from rat cerebral cortex, in both in vitro and ex vivo experiments. The same lithium treatments also abolished guanine nucleotide modulation of agonist binding. Our findings suggest G proteins (Gs and Gi or Go) as the molecular site of action for both the antimanic and antidepressant effects of lithium.
Animals↗
Phosphate Starvation Inducible Metabolism in Lycopersicon esculentum: II. Characterization of the Phosphate Starvation Inducible-Excreted Acid Phosphatase.
Three-day-old suspension cultured cells of Lycopersicon esculentum transferred to a Pi-depleted medium had 2.7 times the excreted acid phosphatase (Apase) activity of cells transferred to a Pi-sufficient medium. Cell growth during this time period was identical for the two treatments. Excreted Apase activity was resolved into two fractions on a Sephadex G-150 column. Most of the phosphate starvation inducible (psi) enhancement in activity was in the lower molecular weight fraction. These two fractions exhibited different substrate versus pH activity profiles. With a native polyacrylamide gel electrophoresis assay, the lower molecular weight fraction resolved into two bands of activity. Both column fractions resolved into the same single band of activity with sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The apparent molecular weight of this enzyme was 57 kilodalton. These data indicate that L. esculentum has at least two isozymes of the psi-excreted Apase and that these isozymes may associate to form high molecular weight aggregates. Labeling studies using [(35)S]methionine show that the psi response in tomato cells is complex and involves changes in the steady state levels of several excreted proteins.
Journal Article↗
Effect of adrenergic agonists on eicosanoid output from isolated rabbit choroid plexus and iris-ciliary body.
Prostanoid production by rabbit choroid plexus (CP) and iris-ciliary body (ICB), and the effects of adrenergic agonists thereon, were studied in vitro. Immunoreactive prostaglandin (PG) E2 was the major prostanoid released by both tissues; the output from ICB was some two orders of magnitude greater than from CP. Immunoreactive 6-keto PGF1 alpha and thromboxane (TX) B2, the dehydration products of prostacyclin and TXA2, respectively, were detected in smaller quantities. Epinephrine stimulated the outputs of PGE2 and 6-keto PGF1 alpha, but not of TXB2, from both tissues. ICB responded to epinephrine concentrations of 10(-4) and 10(-5), while only 10(-4) was effective in stimulating prostanoid synthesis in the CP. Phenylephrine, an adrenergic agonist, stimulated prostanoid output from the ICB, but not from the CP. It is concluded that adrenergic mechanisms stimulate the biosynthesis of prostanoids in the rabbit CP and ICB. The implications of such interactions to aqueous humor and cerebrospinal fluid dynamics, or to other processes in brain and ocular physiology, are discussed.
6-Ketoprostaglandin F1 alpha↗
Effect of exercise and heat exposure on percutaneous absorption of methyl salicylate.
The effects of exercise, heat exposure or both on the percutaneous absorption of methyl salicylate were studied in 6 healthy volunteers. Exercise was performed to 30% of VO2max, 45 min each hour for 6 h, at ambient temperatures of 22 degrees C or 40 degrees C. Systemic availability was assessed by measurement of plasma salicylate concentrations and cumulative urinary salicyluric acid excretion over an 8-h collection period. The absorption of methyl salicylate was increased to more than 3-times above control in subjects exercising in the heat. It is concluded that exercise and heat exposure, by increasing skin temperature, hydration and blood flow, enhance the percutaneous absorption of methyl salicylate.
Adult↗
Effect of verapamil on prostaglandin E2 synthesis by hydronephrotic rabbit cortical interstitial cells in primary culture.
The effect of the calcium channel blocker verapamil on prostaglandin (PG) E2 production by hydronephrotic cortical interstitial cells in primary culture was investigated. Verapamil displayed a dual action, maximally enhancing PGE2 production from 1.2 +/- 0.2 to 30.7 +/- 4.3 ng/ml at 30 microM, whereas at higher concentrations the effect tapered down to base line. Stimulation of PGE2 synthesis by verapamil required extracellular calcium, but was unaffected by the intracellular calcium inhibitor 8-(Diethylamino)octyl 3,4,5-trimethoxy-benzoate or the calmodulin inhibitor trifluoperazine. Other calcium channel blockers, nifedipine and diltiazem, failed to stimulate PGE2 synthesis, implying that this effect of verapamil was unrelated to its commonly recognized action to inhibit calcium channels. However, stimulation by verapamil was inhibited by quinacrine (mepacrine), suggesting a mechanism involving activation of a phospholipase. In addition, verapamil attenuated the bradykinin- or ionophore A23187-stimulated PGE2 production, but it did not alter arachidonic acid-induced PGE2 synthesis. These observations indicate that, in addition to phospholipase activation, verapamil may also act to inhibit phospholipase activity. Inhibition was concentration-dependent over the range 3 to 300 microM, and was reversible. It is concluded that verapamil, at different concentrations, exerts a dual action on cellular phospholipase activity, thereby stimulating, and in turn inhibiting, PGE2 synthesis by hydronephrotic interstitial cells.
Animals↗
Eicosanoid synthesis by rabbit hydronephrotic cortical interstitial cells in culture.
Rabbit hydronephrotic cortical interstitial cells in primary culture were labeled with [1-14C]arachidonic acid and the eicosanoids released after stimulation with bradykinin or A23187 were studied by reverse-phase high performance liquid chromatography. The major arachidonic acid metabolite formed was prostaglandin (PG)E2, comprising more than 30% of the total radioactivity released. 12-Hydroxyheptadecatrienoic acid, probably representing spontaneous breakdown of the cyclic endoperoxides PGG2 and/or PGH2, made up 10 to 15% of the radioactivity released. Other cyclooxygenase products that were released included PGF2 alpha, PGD2, 6-keto PGF1 alpha and only minute amounts of thromboxane B2. Small quantities of the lipoxygenase products 15-, 12- and 5-hydroxyeicosatetraenoic acids (HETEs) as well as leukotrienes (LT)B4, LTC4 and LTD4 were also identified. Significantly larger quantities of 15- and 5-HETEs were recovered at 2 to 5 min than after longer incubations with A23187, suggesting esterification of these HETEs into cellular phospholipids. The data indicate that interstitial cells of the hydronephrotic kidney synthesize a variety of cyclooxygenase and lipoxygenase products of arachidonic acid, which may contribute to the pathophysiology of hydronephrosis. Moreover, it is suggested that PGG2 and/or PGH2 that are released from these cells may be metabolized further by adjacent kidney cells or circulating blood elements to other eicosanoid products, thus increasing the diversity of eicosanoids synthesized in the hydronephrotic kidney.
Animals↗
Eicosanoid synthesis by cultured human urothelial cells: potential role in bladder cancer.
Prostaglandin (PG) H synthase and eicosanoid products of arachidonic acid metabolism have been implicated in several steps in the carcinogenic process. This study assessed these parameters using primary cultures of human urothelial cells. To determine the possible presence of permeability barriers to agonist stimulation, incubations were performed with adherent cells in the presence or absence of thioglycolate pretreatment or with cell suspensions. No evidence for permeability barriers was observed. With adherent cells in the absence of thioglycolate, radioimmunoassayable PGE2 was stimulated by epinephrine less than 12-O-tetradecanoylphorbol-13-acetate = thrombin less than bradykinin = A23187 much less than arachidonic acid. Tumor promoters but not non-tumor promoters stimulated PGE2 synthesis. 1-Oleoyl-2-acetylglycerol which like 12-O-tetradecanoylphorbol-13-acetate activates protein kinase C also increased PGE2 synthesis. Cells prelabeled with [14C]arachidonic acid were exposed to agonists and the profile of eicosanoids synthesized was assessed by high performance liquid chromatography. With bradykinin, the pattern of eicosanoids synthesized was 6-keto-PGE1 alpha (12% of total 14C label), thromboxane B2 (0.4%), PGF2 alpha (1.7%), PGE2 (18%), PGD2 (1%), leukotrienes (0.4 to 1%), 12-hydroxy-5,8,10-heptadecatrienoic acid (3%), 15-hydroxy-5,8,11,13-eicosatetraenoic acid (4%), 12-hydroxy-5,8,10,14-eicosatetraenoic acid (0%) and 5-hydroxy-5,8,12,14-eicosatetraenoic acid (2%). Thus, human urothelial cells contain both prostaglandin H synthase and lipoxygenase pathways with the former being more prominent. These pathways may participate in urinary bladder carcinogenesis.
Arachidonic Acids↗