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)

Secretory leukocyte protease inhibitor (SLPI) and elafin are structurally similar, low-molecular-weight antiproteases produced in the lung. We have developed a simple method for distinguishing the antiprotease activities of SLPI and elafin in lung lavage fluid from those of alpha 1-antitrypsin (alpha 1-AT) that is based on the resistance of the low-molecular-weight antiproteases to inactivation by cetyltrimethylammonium bromide. In a study of 23 healthy, nonsmoking volunteers, we found that the low-molecular-weight antiproteases accounted for 22 +/- 2% (mean +/- SEM, n = 23) of the total neutrophil elastase-inhibitory capacity of human bronchoalveolar lavage fluid (BALF). Elafin activity was below the limit of detection. SLPI activity (as measured by inhibition of alpha-chymotrypsin) accounted for 72 +/- 4% (mean +/- SEM, n = 23) of the low-molecular-weight antiprotease activity in BALF. Measurements of SLPI in the lavage fluid samples by enzyme-linked immunosorbent assay (ELISA) agreed closely with values obtained by measuring the activity of this inhibitor. The activity of the low-molecular-weight antiproteases decreased significantly (p < 0.05), from 9.0 +/- 0.8 to 7.0 +/- 0.6 pmol of neutrophil elastase inhibited per mL (mean +/- SEM, n = 23), following acute ozone exposure.
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PMID:Contribution of secretory leukocyte proteinase inhibitor to the antiprotease defense system of the peripheral lung: effect of ozone-induced acute inflammation. 758

Native LDL and LDL oxidized under various conditions were compared in terms of their ability to activate platelets. Native LDL did not induce platelet shape change or aggregation, even at high concentrations (2 mg protein/mL). LDL was mildly oxidized with either CuSO4 (mox-LDL) or 3-(N-morpholino)sydnonimine (SIN-1-LDL). Analysis of mox-LDL and SIN-1-LDL showed a small increase of dienes (E234nm from 0.28 +/- 0.04 to 0.55 +/- 0.09, mean +/- SD) and thiobarbituric acid-reactive substance (from 0 to 10.6 +/- 1.5 nmol/mg, mean +/- SEM), no change in apo B electrophoretic mobility, and a minor (12% to 30%) decrease in polyunsaturated fatty acid content. Interestingly, this small oxidative modification of LDL dramatically changed its effect on platelets. Irreversible aggregation and secretion were induced by a threshold concentration of 0.4 mg protein/mL. In contrast, LDL thoroughly oxidized with CuSO4 (ox-LDL) did not aggregate platelets. Although mox-LDL was depleted in antioxidants (alpha- and gamma-tocopherol, alpha- and beta-carotene, and other carotenoids), incubation of mox-LDL with exogenous alpha-tocopherol did not reverse its ability to induce platelet aggregation and secretion. Preincubation of platelets with the cyclooxygenase inhibitor aspirin or the phospholipase A2 inhibitors trifluoperazine, quinacrine, 4-bromophenacyl bromide, and propranolol completely prevented platelet aggregation and secretion caused by mox-LDL or SIN-1-LDL. These results indicate that mildly oxidized LDL activates platelets through a phospholipase A2/cyclooxygenase-dependent pathway. The complete inhibition of mox-LDL-induced platelet aggregation by aspirin could contribute to its beneficial effect in cardiovascular disease.
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PMID:Mildly oxidized LDL induces platelet aggregation through activation of phospholipase A2. 762 6

Histamine release has been implicated in the pathogenesis of exercise-induced asthma (EIA), and is believed to be partly mediated by vagal stimulation. Our aim was to determine the relationship between the contributions of vagal stimulation (determined by the use of the muscarinic receptor antagonist, ipratropium bromide) and histamine release (determined by the use of the histamine H1-receptor antagonist terfenadine) in EIA. Ten stable asthmatic subjects with documented EIA took part in a randomized double-blind study. Each undertook four identical treadmill exercise tests, following drug therapy with one of the following: nebulized ipratropium bromide, 0.5 mg, terfenadine, 180 mg, by mouth, both active drugs together, and placebo preparations by mouth and by nebulizer. The mean +/- SEM maximum percentage fall in forced expiratory volume in one second (FEV1) after exercise following placebo therapy was 33.6 +/- 3.8%, which significantly decreased to 27.2 +/- 3.6% after terfenadine, to 21.8 +/- 3.9% after ipratropium bromide, and to 15.1 +/- 4.1% after the combination of both drugs. The addition of ipratropium bromide to terfenadine treatment improved on the protection offered by terfenadine alone. We conclude that both histamine release and vagal stimulation contribute independently and additively to EIA.
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PMID:The contribution of histamine release and vagal reflexes, alone and in combination, to exercise-induced asthma. 822 21

Exogenous peptide YY (PYY) decreases pancreatic exocrine secretion, pancreatic endocrine function, and pancreatic blood flow. We hypothesized that pancreatic cancer cell growth may be inhibited by PYY and a new synthetic analog, BIM-43004-1. Two human pancreatic ductal adenocarcinomas, PANC-1 and Mia PaCa-2, were examined in tissue cultures. Viable pancreatic cancer cells were counted with trypan blue on a hemocytometer slide. Cells (10K, 20K, 40K, and 80K) were cultured and allowed to grow for 36 hr (n = 14/cell concentration). Pancreatic cancer cells received either PYY or BIM-43004-1 at various concentrations. Control tissue cultures received an equivalent volume of saline inoculation. After incubation with the above peptides for 24 hr, MTT tetrazolium bromide was added to assay mitochondrial activity of pancreatic cancer cells in response to PYY and its analog. MTT assay reveals a significant decrease in pancreatic cancer cell growth when PYY and BIM-43004-1 are added to the cell culture. Results in Mia PaCa-2 reveal a 24% cell growth reduction after exposure to PYY and a 23% reduction in cell growth when treated with BIM-43004-1. In PANC-1 cells, a 25% reduction in growth of cells is noted after PYY treatment and a 24% reduction in growth after BIM-43004-1 treatment. (means +/- SEM, P < 0.05 by Student's t test). Our results reveal a significant reduction in human ductal pancreatic cancer growth when treated with either PYY or its analog, BIM-43004-1. These agents may be useful hormonal adjuncts in the chemotherapy of pancreatic adenocarcinoma.
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PMID:Human pancreatic cancer growth is inhibited by peptide YY and BIM-43004-1. 779 50

Collagen type I was purified from equine skin and flexor tendon, and type II collagen was purified from equine articular cartilage. The proteoglycans in these tissues were extracted, using guanidine HCl; the collagens were solubilized, using pepsin digestion, then were selectively precipitated with NaCl. Gel electrophoresis indicated that the precipitates contained only type I or type II collagen. Amino acid analysis indicated that collagen constituted > 97% of the total protein in the precipitates. Hydroxylation of proline was 42.0 +/- 0.6% (mean +/- SEM) in alpha 1(I) and alpha 2(I), and was 48.1 +/- 1.3% in alpha 1(II) chains. The hydroxylation of lysine was 23.2 +/- 0.7% in alpha 1(I) and 34.1 +/- 0.9% in alpha 2(I) chains from tendon, and 49.6 +/- 4.3% in alpha 1(II) chains from cartilage. The cyanogen bromide (CB)-peptide patterns of chromatographically purified equine alpha 2(I) and alpha 1(II) chains were similar to those published previously for rat, bovine, and human alpha 2 and alpha 1 chains. However, the CB-peptide pattern of the equine alpha 1(I) chain resembled the guinea pig alpha 1(I) chain, which has no methionine between CB7 and CB6. Purified equine alpha 1(I)CB7,6 contained no methionine, methionine sulfoxide, or homoserine lactone. Mass of 42.26 kd was determined by use of mass spectrometry, and N-terminal sequence analysis established that the first 12 amino acids of this CB7,6 were identical to the sequence of human alpha 1(I)CB7.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Structure of equine type I and type II collagens. 819 71

Extracorporeal membrane oxygenation (ECMO) is a valuable therapy for the treatment of reversible lung disease in neonates. Associated with this treatment, however, are risks for complications that increase with the duration of therapy. We evaluated alveolar-arterial oxygen tension difference P(A-a)O2 pulmonary compliance (CL), and functional residual capacity (FRC) in 20 infants immediately after ECMO was discontinued, and again 24 hours thereafter. We measured CL by pneumotachography and esophageal manometry and FRC by helium dilution. Mean (+/- SEM) values for CL and FRC increased (CL from 0.28 +/- 0.02 to 0.35 +/- 0.03 mL/cmH2O)/kg and FRC from 18.6 +/- 1.4 to 22.2 +/- 1.1 mL/kg; P < 0.05), and P(A-a)O2 and the oxygenation index (OI) decreased (200 +/- 19 to 169 +/- 14 mm Hg and 6.9 +/- 0.44 to 5.4 +/- 0.5, respectively; P < 0.02), over the 24 hour period following ECMO. Nineteen of 20 infants experienced improvement in at least two of these parameters. Improvements were found to be greatest in the infant with the worst lung function immediately after discontinuing ECMO, and in the ten infants who had not received pancuronium bromide for inducing skeletal muscle paralysis, following decannulation from ECMO. These data indicate that improvement in lung function following ECMO will generally continue over the 24 hour period following the termination of cardiopulmonary bypass, and that borderline pulmonary status may not preclude discontinuation of bypass therapy.
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PMID:Continued pulmonary recovery observed after discontinuing extracorporeal membrane oxygenation. 819 93

The present studies were conducted to evaluate whether apoptosis occurs during spontaneous and prostaglandin F2 alpha (PGF2 alpha)-induced luteolysis and, if so, to determine the relationship between the onset of luteolysis and oligonucleosome formation (a characteristic of apoptosis). In the first study, nine normally cycling heifers were ovariectomized (ovx) during the midluteal phase (day 10 or 15; day 0 = estrus) or after luteal regression (day 19; n = 3/time point). While there was no evidence of oligonucleosome formation in DNA from corpora lutea (CL) collected on days 10 and 15, each CL collected on day 19 exhibited DNA fragmentation, represented by distinct bands of DNA in approximately 185-basepair multiples. In the second study, heifers were ovx (n = 5; controls) or given 25 mg PGF2 alpha 15-16 days after estrus. Heifers receiving PGF2 alpha were subsequently ovx 4, 8, 12, 24, or 48 h (n = 5/time point) after the injection of PGF2 alpha. The concentration of progesterone in venous sera collected at ovx was not different (P > 0.20) in control and 4 h groups, but was decreased (P < 0.01) in the 8, 12, 24, and 48 h groups. Total CL weight (mean +/- SEM; grams) did not change (P > 0.10) from 0 h (controls) to 24 h after injection (range, 3.2 +/- 0.5 to 4.1 +/- 0.6), but decreased (P < 0.06) to 2.0 +/- 0.3 at 48 h. With ethidium bromide (EtBr) staining, no oligonucleosome formation was detected in CL collected from 0-12 h after PGF2 alpha injection. However, pronounced oligonucleosome formation was observed in all 10 CL collected 24 and 48 h after the injection of PGF2 alpha. The absence of oligonucleosomes in 0 and 4 h samples was confirmed by the more sensitive technique of 3'-end labeling of DNA fragments. Some samples in both the 8 and 12 h groups had slight oligonucleosome formation, while all samples in the 24 and 48 h groups showed evidence of intense oligonucleosome formation. Histological analysis of tissue sections indicated an increase (P < 0.001) in the percentage of degenerated luteal cells in the 24 and 48 h groups compared to that in the 0-12 h groups. These data indicate that apoptosis occurs during both spontaneous and PGF2 alpha-induced luteal regression in cattle; however, apoptosis, as indicated by oligonucleosome formation, is not apparent until after serum progesterone concentrations have begun to decrease.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Apoptosis during luteal regression in cattle. 841 26

Inhaled anticholinergic drugs are effective in the treatment of chronic obstructive pulmonary diseases (COPD), of acute asthma, and of some patients with nocturnal asthma. Tiotropium bromide (tiotropium) is a novel anticholinergic agent with a long duration of action and kinetic selectivity for M1- and M3-subtypes of muscarinic receptors. We investigated the duration of protection of a single dose of inhaled tiotropium against methacholine-induced bronchoconstriction in 12 male atopic asthmatic volunteers in a double-blind, placebo-controlled study. On four separate occasions 8 to 24 d apart, methacholine PC20 was measured serially for up to 48 h after placebo and after three doses of tiotropium (10, 40, and 80 microg). Each dose of tiotropium produced mild bronchodilatation as measured by an increase in FEV1 of between 5.5 and 11.1% from baseline, that was sustained for 24 h. There was significant dose-dependent protection against methacholine challenge at 2 h of 5.0 +/- 1.1, 7.1 +/- 0.5, and 7.9 +/- 0.7 (mean +/- SEM) doubling doses after 10, 40, and 80 microg respectively, and this persisted for 48 h. There were no adverse effects reported at any dose. The prolonged bronchodilator response and protection against methacholine challenge suggest that tiotropium may be useful in the treatment of COPD and nocturnal asthma and that once-daily dosing may be sufficient.
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PMID:Prolonged effect of tiotropium bromide on methacholine-induced bronchoconstriction in asthma. 888 78

The neuropeptide galanin (GAL) is widely distributed in the central and peripheral nervous systems where it often coexists with catecholamines and acetylcholine. Recently we have reported that human GAL (hGAL) in man depresses the release of norepinephrine (NE) and the responses to both assumption of upright posture and insulin-induced hypoglycemia. To gain an insight into the action of hGAL on sympathetic nervous system activity in man, we investigated the effects of a 60-min infusion (80 pmol/kg/min) of hGAL or saline on the release of NE, epinephrine (E) and pancreatic polypeptide (PP) induced by an acetylcholinesterase inhibitor, pyridostigmine bromide (PD), in nine healthy volunteers. PD (120 mg orally) induced a significant rise in plasma concentrations of NE (1.6 +/- 0.04 vs. 1.08 +/- 0.06 nmol/l), E (0.34 +/ 0.05 vs. 0.12 +/- 0.04 nmol/l) and PP (178.06 +/- 33 vs. 37.57 +/- 7.35 pmol/l), whilst it significantly reduced heart rate (HR; 61 +/- 2 vs. 71 +/- 4 beats/min). Changes in plasma levels of PP were determined as an indirect measure of amplification of endogenous cholinergic activity produced by PD. Administration of hGAL blunted the release of NE and PP evoked by PD. The mean (+/- SEM) area under the curve produced by PD of NE (50.05 +/- 3.97 nmol/l.90 min) and PP (8,692.87 +/- 1,724 pmol/l.90 min) was significantly (p < 0.001) reduced by hGAL infusion (2.65 +/- 1.57 nmol/l.90 min and 248.1 +/- 148 pmol/l.90 min, for NE and PP, respectively). hGAL failed to affect significantly the E release evoked by PD. hGAL was able to enhance HR significantly (104 +/- 5 vs. 69 +/- 3 beats/min), and completely prevented the PD-induced slowing of HR. Both PD and hGAL did not alter supine systolic and diastolic blood pressure. We conclude that hGAL significantly reduces the release of NE and PP stimulated by PD-induced enhancement of cholinergic activity. These findings are consistent with a functional interrelationship between GAL and the cholinergic system in man, and may suggest the participation of a cholinergic pathway in the galaninergic modulation of the autonomic nervous system.
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PMID:Acute administration of human galanin in normal subjects reduces the potentiating effect of pyridostigmine-induced cholinergic enhancement on release of norepinephrine and pancreatic polypeptide. 893 Sep 40

We have hypothesized that a major role of the apical H(+)-pump in mitochondria-rich (MR) cells of amphibian skin is to energize active uptake of Cl- via an apical Cl-/HCO3(-)-exchanger. The activity of the H+ pump was studied by monitoring mucosal [H+]-profiles with a pH-sensitive microelectrode. With gluconate as mucosal anion, pH adjacent to the cornified cell layer was 0.98 +/- 0.07 (mean +/- SEM) pH-units below that of the lightly buffered bulk solution (pH = 7.40). The average distance at which the pH-gradient is dissipated was 382 +/- 18 microns, corresponding to an estimated "unstirred layer" thickness of 329 +/- 29 microns. Mucosal acidification was dependent on serosal pCO2, and abolished after depression of cellular energy metabolism, confirming that mucosal acidification results from active transport of H+. The [H+] was practically similar adjacent to all cells and independent of whether the microelectrode tip was positioned near an MR-cell or a principal cell. To evaluate [H+]-profiles created by a multitude of MR-cells, a mathematical model is proposed which assumes that the H+ distribution is governed by steady diffusion from a number of point sources defining a set of particular solutions to Laplace's equation. Model calculations predicted that with a physiological density of MR cells, the [H+] profile would be governed by so many sources that their individual contributions could not be experimentally resolved. The flux equation was integrated to provide a general mathematical expression for an external standing [H+]-gradient in the unstirred layer. This case was treated as free diffusion of protons and proton-loaded buffer molecules carrying away the protons extruded by the pump into the unstirred layer; the expression derived was used for estimating stationary proton-fluxes. The external [H+]-gradient depended on the mucosal anion such as to indicate that base (HCO3-) is excreted in exchange not only for Cl-, but also for Br- and I-, indicating that the active fluxes of these anions can be attributed to mitochondria-rich cells.
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PMID:Proton pump activity of mitochondria-rich cells. The interpretation of external proton-concentration gradients. 899 67


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