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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The lamina basilaris of guinea pig cochlea was studied with SEM after trypsin treatment, and with TEM of resin sections and deep-etching replicas. The lamina consists of radial, evenly compacted filaments in the zona arcuata, and radial, discretely bundled filaments in the zona pectinata. In both zones, elementary filaments measured about 12 nm in thickness on the replica. The filaments formed more or less irregular passing bridges with each other and, eventually, a three-dimensional network which was continuous with the basement membrane under the supporting cells.
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PMID:Fine structure of the lamina basilaris of guinea pig cochlea. 829 28

Mast cell mediators are known to contribute to the pathogenesis of asthma. There is some disagreement concerning the numbers of mast cells in asthmatic mucosa. In this study a standardized bronchial brush technique was developed and used to assess intraepithelial mast cells and other inflammatory cells in allergic and nonallergic asthmatic and nonasthmatic subjects. A total of 10 nonasthmatic (5 allergic) and 13 asthmatic (8 allergic) subjects with stable controlled asthma treated with beta-agonist only were assessed by history, spirometry, allergy prick tests, and methacholine airway responsiveness. During fiberoptic bronchoscopy, bronchoalveolar lavage (BAL) was performed from the middle lobe and standardized bronchial brushings were taken from the lingula and left lower lobe bronchi. Quantitative cell counts were performed blind to the clinical characteristics of the subjects. The average total cell recovery from the brushings was 1.04 (SEM 0.09) x 10(6) ml, with a cell viability of 64% (5.3%). Reproducible total cell and mast cell counts were obtained from brushings taken from two lobar bronchi (ICC 0.86). Mast cells were significantly elevated in asthmatic compared with nonasthmatic subjects (1.5 +/- 0.34 versus 0.15 +/- 0.06%). Allergic asthmatic subjects had the greatest numbers of mast cells (1.86 +/- 0.48%); however, the numbers present in brushings from nonallergic asthmatic subjects were also increased (1.03 +/- 0.45%). The mast cells had the staining characteristics of mucosal mast cells, with formalin-blockable metachromatic staining and positive staining for tryptase. Both asthmatic groups also had elevated BAL eosinophils, and neutrophils were elevated in nonallergic asthmatic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intraepithelial mast cells in allergic and nonallergic asthma. Assessment using bronchial brushings. 831 19

We studied the effect of intravenous infusion of synthetic truncated GLP-1 (proglucagon 78-107-amide) on fasting and postprandial gastric acid secretion, gastric emptying, and pancreatic secretion of trypsin and lipase in eight normal volunteers using marker dilution and aspiration technique. The infusion resulted in a plasma concentration of 110 +/- 14 pmol/liter (mean +/- SEM). Truncated GLP-1 significantly inhibited postprandial acid secretion by 43 +/- 11% in spite of unchanged plasma gastrin concentration. Gastric emptying rate decreased significantly; 50% emptying time increased from 16 +/- 2 min to 30 +/- 5 min. Postprandial trypsin and lipase outputs were significantly inhibited by 47 +/- 17% and 40 +/- 9% during truncated GLP-1 infusion. Pancreatic enzyme output was linearly correlated to gastric emptying, and truncated GLP-1 did not affect this relationship, suggesting that the effect on pancreatic secretion was secondary to the effect on gastric emptying. Postprandial insulin and glucagon concentrations were similar with and without truncated GLP-1 infusion in spite of significantly lower blood glucose levels (5.2 +/- 0.2 versus 3.7 +/- 0.3), indicating that GLP-1 stimulated insulin secretion and inhibited glucagon secretion. In conclusion, our results suggest that truncated GLP-1 act as a physiological inhibitor of gastric and pancreatic functions in man.
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PMID:Truncated GLP-1 (proglucagon 78-107-amide) inhibits gastric and pancreatic functions in man. 846 65

In this study we evaluated the effect of several trypsin inhibitors (p-aminobenzamidine: pAB; N-alpha-p-tosyl-L-lysine-chloromethyl-ketone: TLCK and p-nitrophenyl-p'-guanidino-benzoate: NPGM) on sperm binding and penetration of the human zona pellucida. Motile spermatozoa, selected by a two-step Percoll gradient, were incubated at 1 x 10(7) cells ml-1 at 37 degrees C and in 5% CO2 for 4.5 h. This was followed by the addition of 1 mmol pAB l-1 or phosphate-buffered saline (control) for 30 min. Three to four non-viable human oocytes were then added to each sperm suspension and incubated for 3 h. The numbers of spermatozoa bound to the human zona pellucida and in the perivitelline space were determined by phase contrast microscopy. The results showed that pAB significantly inhibited zona penetration by spermatozoa (56 +/- 8% oocytes penetrated, control versus 0 +/- 0% oocytes penetrated, pAB, mean +/- SEM), without modifying spermatozoa-zona pellucida binding. The inhibition of zona penetration was due to a block of the acrosome reaction normally induced by the human zona pellucida. In separate experiments, sperm suspensions pretreated with 1 mmol pAB l-1 or 10 mumol NPGB l-1 exhibited a marked decrease in the percentage of acrosome reactions on the zona surface (85 +/- 4% and 76 +/- 3% inhibition, respectively). In addition, the inhibitors prevented the acrosome reaction induced by human follicular fluid (percentage of acrosome-reacted spermatozoa: control 8 +/- 2; follicular fluid 25 +/- 3; pAB 6 +/- 2; NPGB 8 +/- 1; TLCK 12 +/- 2).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of the acrosome reaction by trypsin inhibitors and prevention of penetration of spermatozoa through the human zona pellucida. 846 8

To determine the feasibility of cellular and biochemical analysis of sputum induced after inhalation of hypertonic (3%) saline, we analyzed sputum induced in 10 healthy and in 18 asthmatic subjects. We also analyzed saliva samples from all subjects. The entire sputum sample and the saliva sample were reduced using dithiothreitol, and cell counts and differentials were determined. Biochemical analysis was performed on sputum and saliva supernatants obtained after centrifugation. We found that induced sputum from asthmatic subjects had a higher percentage of eosinophils [8.1 +/- 3.43 (mean +/- SEM) versus 0.03 +/- 0.02%, p < 0.009] (after excluding squamous cells) and also had higher levels of albumin (232.3 +/- 54.8 versus 79.5 +/- 9.7 micrograms/ml, p < 0.02), fibrinogen (44.2 +/- 11.6 versus 11.9 +/- 2.5 micrograms/ml, p < 0.008) and eosinophil cationic protein (ECP) (142.6 +/- 34.2 versus 26.1 +/- 4.7 ng/ml, p < 0.006) but not of histamine or tryptase. In saliva, squamous cells made up more than 99% of the cells in both groups, and protein concentrations were not significantly different. We conclude that cellular and biochemical analysis of induced sputum is feasible in healthy and in asthmatic subjects and that it reveals differences similar to those reported from analyses of bronchial lavage fluid.
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PMID:Cellular and biochemical analysis of induced sputum from asthmatic and from healthy subjects. 848 20

In order to further characterize low density lipoprotein (LDL)-platelet interaction, we investigated the effect of protease pretreatment of human platelets on the subsequent binding of iodinated LDL (125I-LDL). Our results showed that the platelet LDL receptor had a proteolytic susceptibility different from that of both classical LDL receptors and the fibrinogen receptor. Platelet pretreatment with chymotrypsin, trypsin, and pronase (at 50 micrograms/mL) had no effect on 125I-LDL binding, whereas fibroblast 125I-LDL binding was markedly reduced. Mild proteolytic digestion, however (up to 1 mg/mL), was helpful in characterizing the platelet LDL receptor. Scatchard analysis showed that chymotrypsin did not modify LDL binding characteristics, whereas trypsin and pronase altered maximal number of binding sites (Bmax) without variation in dissociation constant. Trypsin increased Bmax approximately twofold (2156 +/- 327 binding sites on control platelets vs. 5246 +/- 296 on treated platelets, P < 0.001, mean +/- SEM, n = 5), but pronase decreased Bmax about 50% (2017 +/- 275 control vs. 1153 +/- 195 treated, P < 0.001). A minimum of 30 min preincubation was required to detect significant effects, and apparent equilibrium was reached by 60 min. Maximal increase in platelet LDL binding sites induced by trypsin was observed at a protein concentration of 1 mg/mL at 37 degrees C, whereas at 4 degrees C no effect was found. In contrast, maximal pronase-inhibitory effect also was observed at 37 degrees C but at higher protein concentration (10 mg/mL). Aprotinin, phenylmethylsulfonylfluoride, and soybean trypsin inhibitor were capable of fully blocking both the stimulation and the inhibition of platelet LDL binding induced by trypsin and pronase, respectively. Platelet pretreatment with both chymotrypsin and pronase (0.5 mg/mL) activated fibrinogen binding sites to a similar extent as ADP (100 microM). Furthermore, LDL (at a protein concentration of 0.3 mg/mL) increased by 81 +/- 6% the binding of fibrinogen to both protease- and ADP-stimulated platelets, but was unable to activate fibrinogen binding sites in unstimulated platelets. Overall, the results suggest that platelet LDL receptor presents a different proteolytic susceptibility in comparison with both "classical" LDL receptor and fibrinogen receptor.
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PMID:Proteolytic susceptibility of platelet low density lipoprotein receptor. 853 80

A critical component in the regulation of thrombus formation and clearance is the balance between tissue plasminogen activator (tPA) and plasminogen activator inhibitor type-1 (PAI-1). An increase in the plasma concentration of PAI-1 has been proposed as a risk factor in thrombotic disease. Inhibition of PAI-1 activity may have utility in the treatment of thromboembolic disease. We report here the evaluation of three diketopiperazine-based low molecular weight inhibitors of PAI-1 activity (XR334, XR1853 and XR5082). In vitro these compounds reversed the inhibitory effects of PAI-1 against both tPA and urokinase (UK) (IC50: 5 to 80 muM). In contrast, other serpin-serine protease interactions, including alpha 1-antitrypsin-trypsin, alpha 2-antiplasmin- plasmin and antithrombin-thrombin, were not affected, neither did these inhibitors affect global tests of haemostasis. In the light of this promising in vitro profile these compounds were evaluated in a standard radioisotopic assay of clot lysis in whole rat blood following intravenous administration. In this assay these compounds dose-dependently enhanced fibrinolysis ex vivo. After intravenous bolus administration XR334, XR1853 and XR5082 at 5 mg/kg increased clot lysis by 32.0 +/- 5.1% SEM (n = 25, p < 0.01), 36.7 +/- 3.5% SEM (n = 36, p < 0.01) and 60.0 +/- 2.8% SEM (n = 17, p < 0.01) respectively compared to vehicle. Intravenous infusion of these compounds (1 mg/kg/min for 20 min) significantly prolonged (approximately twofold) the time to blood vessel occlusion in the rat electrically-stimulated carotid artery thrombosis model. Thus, these low molecular weight inhibitors of PAI-1 activity enhanced fibrinolysis ex vivo and protected against thrombus formation in the rat.
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PMID:Evaluation of a low molecular weight modulator of human plasminogen activator inhibitor-1 activity. 872 28

Bradykinin and beta-endorphin increases during acute pancreatitis are thought to contribute to the development of hypotension and myocardial depression in acute pancreatitis. beta-Endorphin release is mediated by trypsin-like enzymes and bradykinin from the pituitary gland. This study was undertaken to investigate the effect of a long-acting bradykinin receptor antagonist on bradykinin and beta-endorphin release and on hemodynamic changes during acute pancreatitis. Pancreatitis was induced by the injection of autologous bile mixed with trypsin into the main pancreatic duct after ligation of the accessory duct. Serum bradykinin and plasma beta-endorphin levels and cardiovascular function were measured. Twelve dogs (control group) were given 10 ml/kg/h of lactate Ringer's solution intravenously beginning 1 h before the induction of pancreatitis and continuing throughout the experiments. Six dogs received an intravenous infusion of 0.6 mg/kg/h of a new bradykinin receptor antagonist, HOE 140, D-Arg-[Hyp3, Thi5, D-Tic, Oic8]-bradykinin, in lactate Ringer's solution soon after the induction of pancreatitis. Six of twelve dogs in the control group, and none of the six dogs in the bradykinin receptor antagonist group, died during the experiments. Serum bradykinin levels in both groups increased until 1 h after the induction of pancreatitis, but thereafter the levels in the bradykinin receptor antagonist group decreased gradually until 5 h after induction, and levels were significantly lower than those in the control group (p < 0.05). Plasma beta-endorphin levels in the control group increased significantly, to 291.8 pg/ml (+/- 6.6 SEM) 5 h after the induction of pancreatitis, from the mean levels of 47.8 pg/ml before the induction of pancreatitis, while the mean beta-endorphin level in the bradykinin receptor antagonist group did not increase after the induction of pancreatitis. Infusion of the bradykinin receptor antagonist improved survival rates, hypotension, myocardial depression, and plasma lactate, suggesting that the bradykinin receptor antagonist inhibited the release of bradykinin and beta-endorphin, which contributed to the clinical improvement.
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PMID:Effects of bradykinin receptor antagonist on the release of beta-endorphin and bradykinin and on hemodynamic changes in a canine model of experimental acute pancreatitis. 892 25

A primary culture system of chicken hepatocytes was developed to study the effects of genetic, hormonal and nutritional factors on hepatic triglyceride (TG) secretion in the chicken, and the effect of insulin on TG synthesis and secretion examined. TG synthesis and secretion was measured using [3H]-glycerol incorporation into cellular and secreted TG. An additional step consisting of brief incubation of the monolayer with trypsin solution to improve harvesting the medium immediately adjacent to the cell monolayer, is also proposed. In our culture system, TG secretion occurred at least up to 75 hr of culture, showing a maximum between 40 and 60 hr of culture. No significant effect of insulin could be observed after 24 hr of culture. A clear stimulatory effect was observed with 10(-9) M insulin concentration after 48 hr. The mean ratio of the secretion rates in the presence or absence of insulin was 2.20 +/- 0.30 (SEM, n = 4). In contrast, the 10(-6) M concentration of insulin had no effect on TG secretion. The use of an additional trypsinization step enhanced the findings obtained by simple removal of the culture medium: a clear stimulatory effect of insulin on TG synthesis was observed after both 24 and 48 hr of culture. Analysis of TG fatty acid composition showed an imbalance of monoene versus saturated fatty acids between cellular and secreted TG, secreted TG being more monounsaturated than cellular TG. These results were obtained in the absence of exogenous fatty acid. An oleic acid supplement in the culture medium did not significantly influence TG secretion. In summary, a primary culture system for chicken hepatocyte was developed. A high level of TG secretion was seen in these cells with or without exogenous fatty acid and this secretion was stimulated by insulin. It was concluded that chicken hepatocytes in primary culture provide a useful model for studying regulation of TG secretion.
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PMID:Effect of insulin on triacylglycerol synthesis and secretion by chicken hepatocytes in primary culture. 902 54

To investigate the mechanisms of anaphylactoid reactions to protamine, we have examined the in vitro effects of increasing concentrations of protamine (10(-6)-3 x 10(-4) mol litre-1) on the release of preformed (histamine and tryptase) and de novo synthesized (peptide leukotriene C4 (LTC4) or prostaglandin D2 (PGD2)) mediators from human basophils and mast cells isolated from lung parenchyma, heart, skin and synovial tissues. Protamine 10(-6)-3 x 10(-4) mol litre-1 induced release of histamine, but not de novo synthesis of LTC4 from basophils. At concentrations from 10(-5) to 3 x 10(-4) mol litre-1 it induced histamine release from human heart (mean 6.5 (SEM 1.5)%), skin (17.7 (4.1)%) and to a lesser extent from synovial mast cells, but not from lung mast cells. Protamine also caused the release of tryptase from heart mast cells (12.8 (3.2) micrograms/10(7) cells), but did not induce de novo synthesis of LTC4 and PGD2 from lung and skin mast cells. In these experiments cross-linking of IgE by anti-IgE caused release of LTC4 or PGD2 from human basophils or mast cells. These results demonstrate that protamine acted as an incomplete secretagogue, causing the release of preformed mediators from human basophils and mast cells.
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PMID:Heterogeneous effects of protamine on human mast cells and basophils. 921 27


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