Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of auranofin, an oral chrysotherapeutic agent, on histamine release from human basophils was studied. Auranofin inhibited IgE-mediated, anti-IgE-induced histamine release in a dose-dependent fashion with a concentration of drug required to produce 50% inhibition of 1.3 micrograms/ml. This compound also inhibited calcium ionophore A23187 and 12-0-tetradecanoyl-phorbol-13-acetate-induced histamine release with a concentration of drug required to produce 50% inhibition of 1.7 micrograms/ml and 0.9 micrograms/ml, respectively. Auranofin was less active for formyl-L-methionyl-L-leucyl-L-phenylalanine-induced release of histamine with 32 +/- 10% (mean +/- SEM) inhibition at 2 micrograms/ml. Auranofin effects were reversible when leukocytes preincubated with auranofin was washed with buffer. In contrast, gold sodium thiomalate enhanced IgE-mediated histamine release, suggesting that these two compounds exert their actions at different levels. These results suggest that auranofin may be beneficial to patients with allergic diseases such as bronchial asthma.
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PMID:Auranofin, an oral chrysotherapeutic agent, inhibits histamine release from human basophils. 620 6

In a controlled cross-over trial, we have compared a conventional 40-g protein diet (30 g animal and 10 g vegetable, diet A) with an 80-g vegetable-protein-supplemented diet (30 g animal and 50 g vegetable, diet B) in the treatment of six patients with chronic stable portal systemic encephalopathy, requiring dietary and lactulose therapy. Each diet was given, in random order, for 5 days in hospital. EEG, clinical indices of encephalopathy, and the plasma amino acid profile were assessed at the end of each treatment period. The increase in vegetable protein intake was associated with minor improvement in EEG and clinical performance in two patients, and no change in the others. Fasting plasma phenylalanine and tyrosine were higher on diet B [phenylalanine 108.6 +/- 9.3 (SEM) mumol/L versus 99.6 +/- 8.37, p less than 0.05 (paired t test); tyrosine 153 +/- 15.2 mumol/L versus 140 +/- 14, p less than 0.05). The plasma branched-chain amino acid levels did not change, and the branched chain/aromatic amino acid ratio (BCAA/AAA) was lower on diet B (p less than 0.02). Fecal weights were not significantly altered. These results indicate that patients with chronic portal systemic encephalopathy are tolerant of protein supplementation from vegetable sources. A minor improvement in parameters of encephalopathy was seen in some individuals, despite a lowering of BCAA/AAA which some investigators have thought important in the pathogenesis of encephalopathy.
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PMID:Dietary protein supplementation from vegetable sources in the management of chronic portal systemic encephalopathy. 639 Nov 54

Mean of median phenylalanine intakes of 1- to 6-yr-old treated phenylketonuria patients who were growing normally were evaluated by age, sex, and treatment group assignment. Total daily means of median phenylalanine intakes of subjects in treatment group 1 were significantly different from those of subjects in treatment group 2 except at the median age of 69 months. Total daily phenylalanine intakes varied from 285 +/- 10 to 453 +/- 30 mg (mean +/- SEM) by subjects in treatment group 1. Total daily phenylalanine intakes of subjects in treatment group 2 varied from 349 +/- 12 to 530 +/- 42 mg (mean +/- SEM). Mean, median phenylalanine intakes by males ranged from 30 mg/kg of body weight by the younger to 23 mg/kg of body weight by the older subjects. Means of median phenylalanine intakes of females varied from 32 mg/kg of body weight by the younger to 21 mg/kg of body weight by the older subjects. No child had a median phenylalanine intake below 10 mg/kg of body weight.
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PMID:Phenylalanine intakes of 1- to 6-year-old children with phenylketonuria undergoing therapy. 663 61

Since peritonitis remains a serious clinical problem, we have evaluated the prophylactic efficacy of intraperitoneally administered chemotactic substances in murine intraperitoneal infections. The injection of 10 ml of 3% thioglycollate increased the peritoneal white blood cell count of rats from 1.3 +/- 0.1 X 10(6) (mean +/- SEM) to 1.1 +/- 0.1 X 10(7) (mean +/- SEM) cells/ml. This increase in the number of intraperitoneal phagocytes resulted in reduction in mortality caused by an inoculum consisting of E. coli and hemoglobin from 68% in the control group to 29% in the thioglycollate pretreated group (p less than or equal to 0.02). Intraperitoneal injection of N-formyl-methionyl-phenylalanine (FMP), a chemotactically active oligopeptide, increased the intraperitoneal granulocyte count from virtually 0 to 1 X 1.9 +/- 0.53 X 10(4) (mean +/- SEM) cells/ml after 90 minutes. The rats pretreated in such a manner showed a mortality of 51% after an intraperitoneal challenge with an E. coli/hemoglobin inoculum as compared to a mortality of 72% in control animals (p less than or equal to 0.025). Thus, chemotactic substances can effectively increase the number of phagocytes and concurrently induce resistance to an intraperitoneal bacterial challenge.
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PMID:Chemotactic substances in the treatment of experimental intraperitoneal infections. 700 69

Children with phenylketonuria (PKU) are treated with semi-synthetic diets restricted in phenylalanine. Low or phenylalanine-free formulae provide the majority of protein and energy in the diet while phenylalanine requirements are met by low-protein natural foods. Because of the restriction of natural protein sources in this diet, the study assessed the zinc and copper nutriture of treated children with PKU and correlated linear growth with zinc status. The plasma zinc of the PKU population was 66.6 +/- 3.3 micrograms/dl (mean +/- SEM). The hair zinc was 70.2 +/- 11.5 micrograms/g (mean +/- SEM). The mean plasma and hair zinc of the PKU population were significantly different (p less than 0.05) when compared to normal values of 84.2 +/- 2.9 micrograms/dl and 130.7 +/- 8.3 micrograms/g (mean +/- SEM), respectively. The dietary zinc intake of 10 PKU patients was 8.56 +/- 2.68 mg/day (mean +/- SD). No significant differences (p less than 0.123) were found when the mean zinc intake was compared with recommended dietary allowances for age of 10 mg/day. No significant correlations were found when plasma and hair zinc were plotted with height percentiles. Plasma copper of the PKU subjects (87.6 +/- 6.6 micrograms/dl, mean +/- SEM) was significantly less than that of normal young children (121.5 +/- 3.1 micrograms/dl, mean +/- SEM) despite a copper intake a 1.45 +/- 0.35 mg/day (mean +/- SD).
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PMID:Zinc and copper status of treated children with phenylketonuria. 719 57

The cystic fibrosis transmembrane conductance regulator (CFTR) is an epithelial Cl- channel regulated by protein kinase A. The most common mutation in cystic fibrosis (CF), deletion of Phe-508 (delta F508-CFTR), reduces Cl- secretion, but the fatal consequences of CF have been difficult to rationalize solely in terms of this defect. The aim of this study was to determine the role of CFTR in HCO3- transport across cell membranes. HCO3- permeability was assessed from measurements of intracellular pH [pHi; from spectrofluorimetry of the pH-sensitive dye 2',7'-bis(2-carboxyethyl)-5-(and -6)carboxyfluorescein] and of channel activity (patch clamp; cell attached and isolated, inside-out patches) on NIH 3T3 fibroblasts and C127 mammary epithelial cells transfected with wild-type CFTR (WT-CFTR) or delta F508-CFTR, and also on mock-transfected cells. When WT-CFTR-transfected cells were acidified (pulsed with NH4Cl) and incubated in Na(+)-free (N-methyl-D-glucamine substitution) solutions (to block Na(+)-dependent pHi regulatory mechanisms), pHi remained acidic (pH approximately 6.5) until the cells were treated with 20 microM forskolin (increases cellular [cAMP]); pHi then increased toward (but not completely to) control level (pHi 7.2) at a rate of 0.055 pH unit/min. Forskolin had no effect on rate of pHi recovery in delta F508 and mock-transfected cells. This Na(+)-independent, forskolin-dependent pHi recovery was not observed in HCO3-/CO2-free medium. Forskolin-treated WT-CFTR-transfected (but not delta F508-CFTR or mock-transfected) cells in Cl(-)-containing, HCO3(-)-free solutions showed Cl- channels with a linear I/V relationship and a conductance of 10.4 +/- 0.5 pS in symmetrical 150 mM Cl-. When channels were incubated with different [Cl-] and [HCO3-] on the inside and outside, the Cl-/HCO3- permeability ratio (determined from reversal potentials of I/V curves) was 3.8 +/- 1.0 (mean +/- SEM; n = 9); the ratio of conductances was 3.9 +/- 0.5 (at 150 mM Cl- and 127 mM HCO3-. We conclude that in acidified cells the WT-CFTR functions as a base loader by allowing a cAMP-dependent influx of HCO3- through channels that conduct HCO3- about one-quarter as efficiently as it conducts Cl-. Under physiological conditions, the electrochemical gradients for both Cl- and HCO3- are directed outward, so CFTR likely contributes to the epithelial secretion of both ions. HCO3- secretion may be important for controlling pH of the luminal, but probably not the cytoplasmic, fluid in CFTR-containing epithelia. In CF, a decreased secretion of HCO3- may lead to decreased pH of the luminal fluid.
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PMID:Bicarbonate conductance and pH regulatory capability of cystic fibrosis transmembrane conductance regulator. 751 98

Although there is a growing body of information available regarding restoration of hematopoiesis with peripheral blood stem cell (PBSC) autografts, few studies have explored this procedure using allografts. In this study with healthy donors, we investigated the feasibility of a protocol for mobilizing PBSC using recombinant human granulocyte colony-stimulating factor (G-CSF) and subsequent bulk depletion of T cells from apheresis-harvested cells. Nine informed healthy donors were given G-CSF subcutaneously at two different dosing schedules (5 micrograms/kg/d in five donors and 2 micrograms/kg/d in four) for 5 consecutive days, and serial changes in blood components, including hematopoietic progenitor cells, were monitored. After 5 days of stimulation with G-CSF, PBSCs were collected by apheresis, and yields were compared. The number of white blood cells (WBC) reached a plateau level on either day 2 (5 micrograms) or 3 (2 micrograms), but the numbers of red blood cells and platelets were not affected. Circulating colony-forming unit-granulocyte/macrophage (CFU-GM) levels started to increase 1 or 2 days after the increase in the WBC count. By performing a 3L apheresis, the number of CFU-GM harvested was 4.6 +/- 3.3 x 10(6) (mean +/- standard error of the mean [SEM]) in the 5-micrograms group and 1.8 +/- 0.7 x 10(6) in the 2-micrograms group. Different procedures for depleting T cells, including the use of L-phenylalanine methyl ester (PME) and flasks coated with anti-CD5/CD8 monoclonal antibodies or neuraminidase-treated sheep red blood cells (SRBC), were also tested on the harvested cells. We found that cell lysis with PME before selective removal of T cells was very effective in reducing the number of cells that required further processing and was suitable for routine use. However, our current procedure resulted in unsatisfactory depletion of T cells (99.5% removal) while retaining hematopoietic progenitor cells (7.5% recovery). Further research is required in this area.
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PMID:Cell processing protocol for allogeneic peripheral blood stem cells mobilized by granulocyte colony-stimulating factor. 752 Mar 92

The effects of Na+ and Ca2+ ions on histamine release from human basophils stimulated by anti-IgE, N-formyl-methionyl-leucyl-phenylalanine (FMLP), 4 beta-phorbol 12-myristate 13-acetate (PMA) and Ca2+ ionophore A23187 were evaluated. Isosmotic replacement of Na+ in the extracellular medium with the nonpermeant Na+ analogue choline+ or with glucose led to a significant increase in anti-IgE- (1/5000: 43.7 +/- 7.3% in high Na+ vs 68.9 +/- 7.3% in low Na+, mean +/- SEM, n = 8, P < 0.001), FMLP- (1 microM: 37.9 +/- 2.3% vs 49.5 +/- 4.3%, n = 8, P < 0.01) and PMA-(160 nM: 12.7 +/- 0.9% vs 27.3 +/- 4.3%, n = 8, P < 0.05) induced histamine release, whereas A23187-induced histamine release was reduced (1 microM: 90.4 +/- 2.4% vs 45.4 +/- 3.4%, n = 8, P < 0.0001). The progressive increase in extracellular Na+ concentration was accompanied by a decrease of basophil response to anti-IgE, FMLP and PMA; in contrast, A23187-induced histamine release was up-regulated by Na+. The Na+/H+ exchanger monensin, in the concentration range of 10(-8)-10(-4) M, exerted a dose-dependent inhibitory effect on anti-IgE-, FMLP- and PMA-induced histamine release, but not on A23187-induced histamine release. Extracellular Ca2+ up-regulated the histamine release induced by all the above stimuli. Removal of extracellular Na+ lowered the requirement of extracellular Ca2+ for anti-IgE, FMLP- and PMA-induced histamine release. In contrast with previous observations showing that Na+ supports histamine release from rat peritoneal mast cells and rat basophilic leukaemia cells, these results indicate that Na+ strongly inhibits histamine release from human basophils stimulated by anti-IgE, FMLP and PMA, whereas it enhances Ca2+ ionophore A23187-induced histamine release. The effects of Na+, which are probably related to modulation of membrane potential and/or intracellular pH, vary depending on the cell type and the stimulus employed for cell activation.
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PMID:Ionic regulation of human basophil releasability. III. Effects of Na+ and Ca2+ on histamine release induced by different stimuli. 753 2

We have identified two unrelated girls with chronic neutropenia [absolute neutrophil counts (ANC) 10-870 and 10-940/microL in patients 1 and 2, respectively] and severe defect in superoxide anion generation by granulocytes. Formyl-methionyl-leucyl-phenylalanine-induced superoxide release was 1.2 +/- 0.9 and 1.9 +/- 1.9% (mean +/- SEM, n = 3) of normal controls', mean value in patients 1 and 2, respectively. However, granulocytes from both patients released a normal amount of superoxide upon stimulation with phorbol myristate acetate. Patient 2 exhibited characteristic features of Duane syndrome, a rare disorder of eye movement. Treatment of the patients with recombinant granulocyte colony-stimulating factor led to significant clinical improvements and reduction of infectious complications and to increases in the ANC, to 400-2100/microL in patient 1 and to 500-3000/microL in patient 2. Treatment with 5 micrograms/kg/d resulted in increased intracellular killing of opsonized Staphylococcus aureus by granulocytes and an enhancement of superoxide release upon stimulation with formyl-methionyl-leucyl-phenylalanine in both patients up to 11.1 +/- 6.0 and 13.5 +/- 7.0% (mean +/- SEM, n = 5) of normal controls', mean value in patient 1 and patient 2, respectively. These data suggested that recombinant human granulocyte colony-stimulating factor treatment enhanced resistance to bacterial infection by stimulation of superoxide generation and increasing the bactericidal capacity of peripheral blood granulocytes.
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PMID:Chronic neutropenia and defect in superoxide generation of granulocytes in two patients: enhancement of bactericidal capacity and respiratory burst activity by treatment with recombinant human granulocyte colony-stimulating factor. 753 20

Amino acids adsorbed onto blood cell membranes represent about 8% of the total amino acids in blood. The aim of this study was to determine the in vitro adsorption kinetics of different amino acids (L-alanine, glycine, L-glutamate, L-glutamine, L-phenylalanine and L-leucine) onto rat erythrocyte membranes and to assess the effect of 24-hr starvation on these adsorption kinetics. Isolated red cell membranes were incubated at 37 degrees C for 10 sec in the presence of 14C-amino acids--with different specific radioactivity--the radioactivity retained in the membrane fraction measured and kinetic parameters of amino acid adsorption determined. With the exception of glutamate, where the adsorption was negligible, all amino acids studied were adsorbed onto isolated red cell membranes, adhering to simple Michaelis-Menten kinetics. Km' values of glycine, phenylalanine and leucine adsorption in control rats (14.7 +/- 3.8 mM, 8.41 +/- 0.95 mM and 4.65 +/- 0.46 mM respectively, SEM, n = 6-8) decreased in response to 24-hr starvation, giving the following values: 0.792 +/- 0.122 mM, 5.32 +/- 0.82 mM and 3.53 +/- 0.31 mM respectively (SEM, n = 6-8), Vmax' value of glycine adsorption of control rats decreased (from 61.0 +/- 15.5 mmol/mol P/sec to 4.25 +/- 0.70 mmol/mol P/sec, SEM, n = 7) and that of leucine increased (from 13.5 +/- 1.0 mmol/mol P/sec to 18.9 +/- 2.0 mmol/mol P/sec, SEM, n = 7) as an effect of 24-hr starvation. This study shows that alanine, glycine, glutamine, phenylalanine and leucine, but not glutamate, adsorbed onto erythrocyte membranes according to Michaelis-Menten-like kinetics.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vitro adsorption of amino acids onto isolated rat erythrocyte membranes. 758 9


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