Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both barbiturates and ethanol have been reported to interact with the GABA-benzodiazepine receptor-chloride ionophore 'supramolecular complex'. These observations raise the possibility that some of the pharmacologic actions of barbiturates and ethanol may be mediated through this complex. In this study we have administered a series of drugs which bind to various components of the complex in an attempt to antagonize the lethality of sodium pentobarbital, and ethanol-induced loss of righting reflex in mice. It was found that isopropylbicyclophosphate (IPPO), a cage convulsant which binds at or near the chloride ionophore, greatly reduces the overall mortality (and increases latency to death) of animals pretreated with a lethal dose of pentobarbital. Picrotoxin also decreases pentobarbital lethality, but only at doses which were usually lethal when given alone. Picrotoxin shortened, rather than increased, latency to death. Strychnine did not prevent pentobarbital lethality, suggesting that the IPPO effect is not shared by convulsants in general. IPPO did not prevent ketamine-induced deaths, which supports the notion that the protective actions of IPPO are specific for depressant drugs which act at the chloride ionophore. IPPO also significantly reduced the duration of loss of righting reflex induced by ethanol. These observations suggest that the use of compounds which have a high affinity for the chloride ionophore in vitro might be fruitful in developing a clinical treatment for barbiturate or ethanol toxicity.
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PMID:Are the toxicities of pentobarbital and ethanol mediated by the GABA-benzodiazepine receptor-chloride ionophore complex? 298 19

Sheep with a parotid fistula and sodium-deprived for 24 or 48 h (Na deficit = 500-700 mmol) were trained to drink their entire requirement of sodium bicarbonate solution from a cup in their cage in a single draught for up to 2 min. The cup was connected to a reservoir by an apparatus that enabled the concentration of the solution offered to be changed after the animal had drunk the first 100 or 150 ml of fluid without interrupting the flow of fluid or disturbing the drinking sheep. Under control conditions, the concentrations of solutions in the cup and reservoir were the same, either 900 mM or 300 mM NaHCO3. On experimental days, the concentration of NaHCO3 in the cup and reservoir were different so that the concentration of fluid increased from 300 mM to 900 mM or decreased from 900 mM to 300 mM NaHCO3. On those experimental days when the concentration of NaHCO3 was increased from 300 to 900 mM, the sheep drank a volume of fluid sufficient to maintain intake commensurate with loss. However, when the concentration of NaHCO3 was decreased from 900 to 300 mM, the sheep drank a volume of fluid insufficient to correct the deficit. It is proposed that the failure of sheep to react appropriately to a decrease in NaHCO3 concentration is a consequence of taste adaptation.
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PMID:The role of taste in rapid sodium satiation by sodium-deficient sheep. 303 99

Stress induced by routine cage cleaning causes retention of Na+ and K+, and increased water and prostaglandin metabolite excretion when measured either against concurrent-controls or against self-control values. This novel stress completely masked the diuretic effects of a long-acting prostaglandin synthetase inhibitor previously observed in a stress-free environment. The results show that prostaglandin synthesis and urine volume regulation are closely associated. They also demonstrate a complete dissociation of urine volume and prostaglandin synthesis regulation from electrolyte regulatory mechanisms in a stressful environment.
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PMID:Association of prostaglandin metabolism with urine volume; dissociation from excretion of Na+ and K+ by stress. 308 98

Male Long Evans rats were obtained at 21 days of age and were housed in either an aggregated (four per double cage) or isolated (one per single cage) condition for 6 weeks. They were then placed on a fluid deprivation schedule that allowed them access to fluids for 20 min daily. This schedule was maintained for the remainder of the experiment. Following habituation, sensitivity to morphine-induced conditioned taste aversion (CTA) was compared in the differentially housed rats. On the 1st day and every 5 days thereafter the rats were presented with a 0.1% solution of sodium saccharin for the 20-min drinking period, followed immediately by an injection of morphine (0, 2.5, 5.0, 10.0, or 20.0 mg/kg). On intervening days they received water as the fluid. No drugs were given on these days. There was no difference in baseline saccharin consumption as a function of housing condition. In comparison with the isolated rats, the grouped animals were more sensitive to the CTA-inducing properties of low doses of morphine. These data strengthen the already existing evidence for the influence of the early housing environment on drug sensitivity and provide additional support for the conclusion that variability in response to a number of drugs of abuse can be reduced by environmental means. Possible mechanisms for the differences between isolation and aggregation housed rats are discussed.
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PMID:Isolation housing decreases the effectiveness of morphine in the conditioned taste aversion paradigm. 311 Aug 28

Galactosyltransferase (GT) (EC 2.4.1.38) was purified to homogeneity from human ovarian tumor effusion fluid and normal human serum by chromatography on alpha-lactalbumin and anti-human immunoglobulin affinity (to selectively absorb contaminating IgG) columns. Both preparations showed a single, broad band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis centered at a molecular weight of 48,000, but nondenaturing polyacrylamide gel electrophoresis of GT isolated from tumor effusion fluid revealed the presence of a series of oligomeric proteins possessing GT activity, which were barely detectable in normal human serum. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of N-glycanase- and O-glycanase-treated GT revealed that each endoglycanase removed carbohydrate with an approximate molecular weight of 3,000, revealing the presence of both N-linked and O-linked oligosaccharide substitutions on GT. Purified GT (containing a mixture of GT isoenzymes) was used to immunize BALB/c mice for monoclonal antibody (MAb) preparation. Four of the MAb isolated reacted with GT. MAb 3872 (patent pending; an IgG1) was determined to be specific for a cancer-associated GT isoenzyme (GT-II) by immunostaining of Western blots and nondenaturing polyacrylamide gel electrophoresis of GT specifically eluted from a MAb 3872 affinity column. Two 125I-labeled cyanogen bromide peptides (Mr 8,400 and 7,400) prepared from 125I-GT were specifically bound and eluted from a MAb 3872 affinity column, demonstrating that the MAb 3872 GT-II-specific antigenic epitope resides on these peptides. MAb 3872 was immobilized on 1,1'-carbonyldiimidazole-activated trisacryl GF-2000 and used to specifically assay serum GT-II levels in 29 individual normal human serum samples and 77 serum samples from 38 patients with advanced ovarian tumors. The normal serum GT-II level was found to be 85.3 +/- 30.9 milliunits/ml, with a range of 17 to 160 milliunits/ml. Of the 38 tumor patients, 33 showed GT-II values in excess of 200 milliunits/ml, with a range of 216 to 8,469 milliunits/ml. Serial samples obtained from the ovarian tumor patients suggested that the serum GT-II level reflected the tumor burden of the patient.
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PMID:Characterization and immunoassay of human tumor-associated galactosyltransferase isoenzyme II. 313 19

Phosphohexose isomerase (PHI) derived from human gastrointestinal tumor tissue was isolated by specific elution from a cation exchanger. The identity of three PHI variants in the purified preparation could be demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and isoelectric focusing analysis. By preparative IEF the variants could be resolved to high homogeneity. The monomer of the common major variant with a pI of 9.1 revealed a molecular weight of 60,000, whereas for the cancer-associated variants with a pI of 8.9 and 8.6, a molecular weight of 57,000 and 56,000, respectively, was determined. The results obtained support the hypothesis that those variants are due to a specific intracellular cleavage of the enzyme in the malignant cells. Since it has been shown that the Mr 56,000 protein neuroleukin exhibits a strikingly high degree of homology with PHI (M. Chaput et al., Nature (Lond.), 332: 454-455, 1988; P. Faik et al., Nature (Lond.), 332: 455-456, 1988), the described specific cleavage of PHI might be responsible for the conversion of an enzyme to a trophic factor.
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PMID:Purification and characterization of phosphohexose isomerase from human gastrointestinal carcinoma and its potential relationship to neuroleukin. 319 76

The accumulating evidence that the delivery of fluid from the proximal tubules to the loop of Henle (Vprox) can be measured in conscious rats by the lithium clearance (CLi) technique has renewed interest in developing a method by which also the glomerular filtration rate can be measured in conscious rats in a steady-state condition without influence from anesthesia and surgery. In the present study, Wistar rats of both sexes were put into a restraining cage, catheters were implanted in the jugular vein and the bladder, and renal parameters were determined under various conditions: different types of surgery, absence or presence of infusion with saline or glucose, normal or reversed diurnal rhythm, and examination at various times after surgery. In acutely operated and restrained rats given saline infusion, the proximal tubular fluid output (CLi) as well as the urinary excretion of sodium (UNaV) increased markedly during the first hours after anesthesia and surgery. After 5 h, both variables were significantly higher than in unoperated, unrestrained rats (CLi 364 +/- 40 vs. 151 +/- 38 microliters/min/100 g; UNaV 1,243 +/- 433 vs. 219 +/- 88 nmol/min/100 g; means +/- SD). Reversal of the diurnal rhythm did not change this pattern. Rats infused with 150 mM glucose instead of saline showed similar increases in CLi and UNaV, although the absolute levels were lower than in saline-infused rats. Rats given no infusion at all had subnormal values of CLi and UNaV. Rats operated 1-3 days before experiments and infused with saline showed enhanced although more stable values of CLi and UNaV.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of recovery from anesthesia and surgery on renal sodium handling in conscious rats. 324 93

1. We have previously reported reduced blood pH and plasma bicarbonate in young Okamoto-Aoki spontaneously hypertensive rats (SHR) compared with normotensive Wistar-Kyoto rats (WKY). Acid loading with 1.5% (w/v) NH4Cl as the sole drinking fluid produced identical falls in blood pH, the difference remaining significant. 2. The ability of SHR to excrete acid and alkaline loads was compared with that of WKY under metabolic cage conditions. The effects of such manipulations on urinary sodium, potassium, calcium and phosphate excretion were also determined. 3. No difference was found in the ability to excrete an acid load or to reduce urine pH. Neither total urinary ammonium ion nor titratable acid differed significantly between the strains under either baseline or acid-loading conditions. 4. Baseline urinary bicarbonate excretion was not significantly different between strains but intraperitoneal administration of NaHCO3 at 2.0 mmol/kg body weight resulted in enhanced excretion in the SHR (SHR vs WKY: 625.2 +/- 71.5 vs 381.8 +/- 40.6 mumol 24 h-1 kg-1 body weight, P less than 0.01, mean +/- SEM). 5. No difference in urinary sodium or potassium excretion was observed between SHR and WKY, but basal calcium and phosphate excretion were reduced in SHR (P less than 0.05). 6. Increased urinary bicarbonate excretion in the presence of significantly reduced plasma bicarbonate suggests reduced tubular reabsorption of bicarbonate, which may contribute to the mild metabolic acidosis in young SHR.
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PMID:Pathogenesis of abnormal acid-base balance in the young spontaneously hypertensive rat. 340 22

The effect of high dietary sodium (8%) on blood pressure in spontaneously hypertensive (SHR), borderline hypertensive (BHR), and normotensive Wistar-Kyoto (WKY) rats was determined weekly by tail cuff plethysmography for one week of baseline and four weeks of diet. After 4 weeks, significant elevations in systolic blood pressure were found in SHR and BHR groups, but not in WKY. BHR studied an additional 4 weeks showed a further progression of hypertension, reaching levels nearly equal to control SHR. Direct measurement of arterial pressure in conscious animals in their home cage confirmed the elevation in pressure in both SHR and BHR groups. Metabolic studies revealed that the high sodium diet reduced body weight in SHR and BHR strains, but not in WKY. Although both urinary volumes and sodium excretion values were significantly lower in SHR and BHR compared with WKY, this effect disappeared when adjustments for body weight were made. Plasma norepinephrine determinations revealed a significant response to cold stress in all groups. Plasma epinephrine was elevated in all strains in response to cold stress; however, a consistent statistical elevation was seen only in WKY. The BHR is discussed as a model for determining the triggers responsible for environmentally-induced hypertension.
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PMID:Hypertension produced by a high sodium diet in the borderline hypertensive rat (BHR). 343 73

A method for electron microscopic demonstration of supranucleosomal (20-30 nm chromatin) fiber loops was developed. Chicken erythrocytes were treated with varying concentrations of detergents, such as Joy, sodium N-lauroyl sarcosinate, and sodium laurylsulfate, and then fixed with a formalin solution. The fixed cells were centrifuged onto an electron microscope grid, followed by staining and metal shadowing. Thin-sectioned specimens of the fixed cells were prepared routinely. Although supranucleosomal fiber loops could be observed when any one of these detergents was used, Joy gave the best result. Electron micrographs of rotary-shadowed specimens of erythrocyte ghosts formed by treatment with a low concentration (0.07-0.11 w/w%) of Joy showed a halolike, radial arrangement of supranucleosomal fiber loops around the ghost cells. The width of the halo was about 3 micron. By increasing the detergent concentration (approximately 8% Joy), nucleosome fibers and naked DNA appeared and increased in number, indicating that the supranucleosomal fibers were disassembled by the action of the detergent. Thin-sectioned specimens of cells treated with 0.09% Joy showed granulofibrillar chromatin radially dispersed from the nuclear cage. The fibers were thought to be identical with the supranucleosomal fibers observed in the rotary-shadowed specimens.
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PMID:Chromatin organization in detergent-lysed chicken erythrocyte nuclei. 350 49


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