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)

Formyl-methionyl-leucyl-phenylalanine (FMLP), a synthetic, acylated tripeptide analogous to bacterial chemotactic factors, has been shown to cause bronchoconstriction in guinea pig, rabbit, and human airways in vitro. To determine whether FMLP causes bronchoconstriction in man in vivo, a preliminary study was undertaken in which five non-smokers (mean age 35 years, FEV1 94% (SEM 5%) predicted) and five smokers (mean age 34 years, FEV1 93% (6%) predicted) inhaled aerosols of FMLP. None of the subjects showed airway hyperresponsiveness to histamine (the provocative concentrations of histamine causing a fall of greater than or equal to 20% in FEV1 (PC20) were over 8 mg/ml). FMLP dissolved in 50% dimethylsulphoxide and 50% saline in concentrations of 0, 0.06, 0.12, 0.25, 0.5, 1.0, 2.0, and 4.0 mg/ml was administered to the subjects by means of a French-Rosenthal dosimeter, FEV1 being recorded after inhalation of each concentration. Dose dependent falls in FEV1 occurred in five non-smokers (geometric mean 1.76, 95% confidence limits 0.87-3.53 mg/ml) and three smokers (0.23, 0.07-0.78 mg/ml), with two smokers not responding by 20% to the highest concentration of FMLP. On a separate day the FMLP dose-response curves were repeated after nebulisation of 500 micrograms of ipratropium bromide. The PC20 FMLP in the responders more than doubled. In six additional normal subjects a histamine inhalation test was performed before and four and 24 hours after inhalation of FMLP. All subjects remained unresponsive to histamine. These results show that FMLP is a potent bronchoconstrictor in some non-asthmatic individuals in vivo and this may be important in bronchoconstriction related to infection in patients with chronic obstructive lung disease.
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PMID:Effect of inhaled formyl-methionyl-leucyl-phenylalanine on airway function. 296 25

In the present study we have demonstrated that human peripheral blood granulocytes from elderly subjects exhibit reduced chemotaxis and degranulation in response to stimulation with fMet-Leu-Phe. Cyclic AMP levels in non-stimulated cells were not significantly different (mean +/- SEM): 4.8 +/- 0.6 and 3.9 +/- 0.4 pmol/10(7) cells for young and elderly respectively. Stimulation with fMet-Leu-Phe (5 X 10(-7) mol/l) for 30s induced the production of cyclic AMP: 8.4 +/- 0.5 and 6.7 +/- 0.3 pmol/10(7) cells for young and elderly. These findings, together with those previously published by us, suggest that cyclic AMP production and cellular functions which this molecule participates in are reduced in cells from elderly individuals.
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PMID:Age-related differences in granulocyte chemotaxis and degranulation. 300 6

Hypoxia was induced by exposing rats to an atmosphere of 93% N2, 7% O2 for 4-48 hr. The animals became hypoxic as indicated by a decreased blood PaO2 (mean +/- SEM: 48 +/- 10 mm Hg). Hypoxia was accompanied by metabolic acidosis (pH 7.22 +/- 0.02) and decreased serum bicarbonate levels (9.0 +/- 4.0 meq/liter). Hypoxic rats also showed evidence of tissue hypoxia; liver tryptophan oxygenase levels were increased to 21 +/- 2 nmole/min/mg protein. In the hypoxic animals there was decreased jejunal mucosal (Na+-K+)-ATPase activity and an inhibition of active intestinal transport of sodium, glucose, 3-O-methylglucose, galactose, tyrosine, phenylalanine, and glycine as determined by in vivo perfusion studies. Jejunal fructose transport, which has a large passive component, was unaffected by hypoxia. The electrolyte, carbohydrate, and amino acid transport alterations produced by hypoxia were seen in the absence of an effect on jejunal cell number, DNA synthesis, or cell turnover. There was also no evidence of histological or ultrastructural damage. Furthermore, studies with a luminal macromolecular tracer, horseradish peroxidase, indicated that the jejunal lumen-to-blood barrier to macromolecules was also unaltered in these hypoxic animals. In vitro local oxygenation of the jejunum, by bubbling of 95% O2:5% CO2, markedly improved sodium and glucose (but not 3-O-methylglucose) absorption in hypoxic rats and control rats. The (Na+-K+)-ATPase activity of the jejunal mucosa of hypoxic rats was significantly enhanced by the local bubbling of 95% O2:5% CO2. Overall, our data indicate that during relatively mild conditions of hypoxia there is an inhibition of jejunal (Na+-K+)-ATPase activity and related transport processes that is prevented by in situ oxygenation.
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PMID:Alterations in jejunal transport and (Na+-K+)-ATPase in an experimental model of hypoxia in rats. 300 54

Cerebrospinal fluid (CSF) histidine concentration was significantly elevated in seven patients early in the alcohol withdrawal syndrome (206.3 +/- 74.4 (SEM) nanomols/ml CSF). When these same patients were restudied an average of six days later when alcohol withdrawal was clinically resolved, their mean CSF histidine concentration continued to be significantly elevated (164.7 +/- 24.7) when compared to normal (12.0 +/- 0.5 nanomols/ml CSF). Other amino acids (aspartic acid, serine, alanine, methionine, leucine, tyrosine, phenylalanine, lysine and arginine) showed no definite changes from normal, and no change during the course of alcohol withdrawal. Possible reasons for these high concentrations and the extreme variability (especially early in alcohol withdrawal) are discussed.
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PMID:Elevated cerebrospinal fluid histidine in alcohol withdrawal. 322 84

Tyr-Gly-Gly (YGG) was recently shown to be an extraneuronal metabolite of opioid peptides derived from proenkephalin A, formed in brain by the action of "enkephalinase" (membrane metalloendopeptidase, EC 3.4.24.11) and degraded by aminopeptidases. The dynamic state of YGG in mouse striatum was studied by evaluating the changes in its level elicited by inhibitors of these peptidases. Inhibition of YGG synthesis by Thiorphan or acetorphan reduced YGG levels with a t1/2 (mean +/- SEM) of 12 +/- 2 min, indicating an apparent turnover rate (mean +/- SEM) of 18 +/- 2 pmol/mg of protein per hr. An apparent turnover rate of 18 +/- 2 pmol/mg of protein per hr was derived from the rate of YGG accumulation elicited by the aminopeptidase inhibitor bestatin. In addition, accumulation of Tyr-Gly-Gly-Phe-Met (YGGFM) in an extrasynaptosomal fraction after blockade of its degradation by Thiorphan and bestatin occurred at a rate of 18 +/- 3 pmol/mg of protein per hr, which is likely to reflect the rate of enkephalin release in vivo. Hence, the three series of data suggest that striatal enkephalins rapidly turn over--e.g., with a t1/2 in the 1-hr range. Pentobarbital anesthesia reduced by about 60% the rate of YGG accumulation elicited by bestatin and the extrasynaptosomal YGGFM accumulation elicited by Thiorphan and bestatin. This suggests that the activity of striatal enkephalin neurons is depressed during anesthesia. Pentobarbital (and chloral hydrate) did not affect the steady-state level of YGGFM but rapidly reduced that of YGG. Hence, the steady-state levels of YGG seem a reliable index of changes in enkephalin release, and measuring levels of characteristic fragments might therefore provide a general means of evaluating neuropeptide release in vivo.
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PMID:Steady-state level and turnover rate of the tripeptide Tyr-Gly-Gly as indexes of striatal enkephalin release in vivo and their reduction during pentobarbital anesthesia. 352 54

The effect of flow on the adhesion of polymorphonuclear leukocytes (PMNL) to vascular endothelium was investigated using a parallel plate chamber with a well-defined flow field. Washed PMNL were perfused over a monolayer of primary human umbilical vein endothelial cells (HUVEC) pretreated with formyl-methionyl-leucyl-phenylalanine (FMLP, 1 X 10(-7) mol/L) for five minutes. In other experiments HUVEC were pretreated with interleukin 1 (IL1,2 U/mL) for four hours. PMNL adhesion to stimulated and control HUVEC was measured over a physiologic range of wall shear stresses. PMNL adhesion to nylon-coated surface was also studied. At a wall shear stress of 0.98 dynes/cm2,283 +/- 37.3 PMNL/mm2 (mean +/- SEM) adhered to FMLP-treated HUVEC while 195 +/- 20.3 PMNL/mm2 adhered to control HUVEC. At 1.96 dynes/cm2, 68 +/- 14.1 PMNL/mm2 adhered to FMLP-treated HUVEC and 42 +/- 6.0 PMNL/mm2 adhered to control HUVEC. At 3.92 dynes/cm2, virtually no PMNL adherence was noted on either control or FMLP-treated HUVEC. On IL 1-treated HUVEC at 1.96 dynes/cm2, 371 +/- 25.8 PMNL/mm2 adhered while 28 +/- 2.9 PMNL/mm2 adhered to control HUVEC. PMNL adhesion to IL 1-treated and control HUVEC dropped to 10.2 +/- 3.8 and 6.8 +/- 3.5 PMNL/mm2, respectively, at 3.01 dynes/cm2. The effect of flow on PMNL adhesion appears to be an important factor in determining the outcome of the PMNL/HUVEC adhesive interaction under these experimental conditions.
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PMID:Effect of flow on polymorphonuclear leukocyte/endothelial cell adhesion. 366 36

The chemotactic peptide fMet-Leu-Phe-Lys is a potent chemoattractant for human blood monocytes. However, only one-third of the monocytes respond. To determine whether or not lack of response reflected absence of attractant receptors, we equilibrated peripheral blood mononuclear cells with fMet-Leu-Phe-Lys-FITC and analyzed binding by flow cytometry. The fluoresceinated peptide bound rapidly at 0 degree C, and the amount bound approached saturation with increasing concentration. The percentage of blood monocytes that bound the peptide was 60 +/- 8 (SEM for seven experiments). In contrast, only 36 +/- 3% (SEM for 16 experiments) of monocytes responded to the attractant by directed migration. It follows that, among the 64 nonmigrating monocytes per 100 total monocytes, approximately 40, or two-thirds of them, fail to bind attractant; the remaining one-third bind attractant but do not respond with directed movement.
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PMID:Analysis of human monocyte chemoattractant binding by flow cytometry. 386 52

The purpose of this study was to evaluate the rabbit anterior eye chamber as a quantitative measure of leukotaxis using 51Cr-labeled homologous leukocytes and then to determine the effects of ibuprofen on N-formyl-methionyl-leucyl-phenylalanine (FMLP) -induced leukotaxis. Leukocyte accumulation was assessed at various intervals (0-24 h) after instillation of FMLP (10(-4) M, 40 microliters) and at various doses (FMLP 10(-6)-10(-4) M). New Zealand white rabbits (2.6-3.0 kg) were treated with ibuprofen for three days with the following regimens: 8.0, 17.5, 35.0, 70.0 mg/kg/ day. Leukocyte quantitation was determined using a direct cell count and recovery of 51Cr-labeled leukocytes from anterior eye chamber aspirations 3 h after their injection into the systemic circulation. FMLP induced a dose-dependent accumulation of leukocytes. Leukocyte influx into the anterior eye chamber increased between 2 and 4 h after FMLP instillation, peaking between 4 and 6 h, then resolving after 8 h. Ibuprofen inhibited leukocyte accumulation into the anterior eye chamber in a dose dependent fashion with a maximum (90.0 +/- 1.4%, X +/- SEM) inhibition with 70 mg/kg/day and an ID50 of 8 mg/kg/day. In conclusion, the anterior eye chamber FMLP-stimulated leukotaxis assay is useful to evaluate the role of pharmacologic agents. Here, ibuprofen was found to inhibit leukotaxis in a dose-dependent manner.
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PMID:Modulation of leukotaxis by ibuprofen. A quantitative determination in vivo. 393 Apr

Administration of total parenteral nutrition (TPN) solutions high in branched chain amino acids (BCAA) is thought to improve metabolic support during stress. This prospective, randomized, double blind study compared 45 per cent BCAA with 25 per cent BCAA in 12 patients. Seven patients had multiple trauma; two, gastrointestinal surgery; one, pancreatitis; and two, cirrhosis. The TPN regimen was 1.0-1.5 gm/kg/day amino acids and 30-45 glucose kcal/kg/day. The BCAA formula used was high in isoleucine and valine, but not leucine. Amino acid plasma levels, blood chemistries, 3-methylhistidine excretion, and nitrogen balance were studied. Control studies showed negative nitrogen balance (-7.1 +/- 2.9 gm) (mean +/- SEM), elevated insulin (61 +/- 21 microunit/ml), and elevated 3-methylhistidine (3MH) excretion (688 +/- 309 micromol); plasma leucine (93 +/- 11 nmol/ml) and isoleucine (37 +/- 23) were low, and valine (155 +/- 20) was elevated. Plasma methionine (40 +/- 9) and tyrosine (70 +/- 12) were high normal. Phenylalanine (85 +/- 5) was elevated. Both groups showed increased nitrogen excretion and positive nitrogen balance during the study (25 per cent, 2.0 +/- 1.4 gm/day; 45 per cent, 1.2 +/- 2.6 gm/day). Three-methylhistidine excretion changed little in either group (557 +/- 149, 414 +/- 91), insulin rose (135 +/- 27, 65 +/- 19), and plasma leucine (82 +/- 4, 71 +/- 9) changed little. Plasma isoleucine (51 +/- 3, 155 +/- 16) and valine (173 +/- 11, 691 +/- 23) both rose, more in the 45 per cent group. Methionine (67 +/- 12, 37 +/- 4) and tyrosine (51 +/- 6, 50 +/- 10) changed little.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of total parenteral nutrition with 25 per cent and 45 per cent branched chain amino acids in stressed patients. 393 93

Optimal function of transfused granulocytes (PMNs) requires adequate glycogen metabolism. Previous studies in our laboratory suggested that stored PMNs had decreased glycogen. We report here the glycogen content and chemotaxis of stored PMNs, and the ability of fresh and stored PMNs to use glycogen as the fuel source for chemotaxis. PMNs were prepared from 8 fresh units of blood drawn into citrate-phosphate-dextrose-adenine, suspended at 2 or 8 X 10(7) PMN per ml in autologous plasma with or without 15 mM sodium bicarbonate, and stored at 22 to 24 degrees C in transfer packs for 48 hours. Glycogen was measured on resting PMNs, and after challenge with opsonized zymosan and F-Met-Leu-Phe (FMLP). The chemotaxis of fresh and stored PMNs was measured in the presence or absence of extracellular glucose. Fresh PMNs contained 10.3 +/- 0.5 (mean +/- SEM) micrograms of glycogen per 10(6) PMN. Glycogen decreased by 4.2 +/- 0.9 micrograms per 10(6) PMN after challenge with opsonized zymosan and by 1.1 +/- 0.6 micrograms per 10(6) PMN after FMLP. After 48 hours of storage, neutrophil glycogen increased by 18 percent, except in units stored at a concentration of PMN of 8 X 10(7) per ml without sodium bicarbonate. In PMNs from these units stored without bicarbonate, glycogen decreased by 9 percent (p less than .05), and there was a 19 and 55 percent decrease in the ability of PMN from these units to metabolize glycogen after exposure to opsonized zymosan and FMLP, respectively (p less than 0.05). In addition, in PMNs from units stored at a concentration of PMN of 8 X 10(7) per ml without bicarbonate, there was a 47 and 70 percent decrease in chemotaxis at 24 and 48 hours, respectively (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glycogen metabolism in stored granulocytes. 400 9


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