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)

Cerebrospinal fluid (CSF) from 20 male patients with nonneurologic disease (age 64.5 +/- 2.8 SEM) was analyzed for the presence of the serpin alpha 1-antichymotrypsin (alpha 1-ACT). A chymotrypsin-specific chromogenic substrate (succinyl-Ala-Ala-Pro-Phe-p-nitroanilide) was used to examine the CSF samples. All CSF samples showed inhibitory activity ranging from 45 to 80% inhibition. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the samples revealed the presence of a 68-kDa protein migrating identical to authentic human plasma alpha 1-ACT. Complex formation was performed with iodinated bovine chymotrypsin for several representative CSF samples having the highest chymotrypsin inhibitory activity. Comparison was made with complex formation performed with commercially available authentic human plasma alpha 1-ACT. These studies showed the formation of complexes at 37 degrees C, regardless of whether the sample was subsequently boiled or not. In the case of CSF, two complex bands, mass smaller than with plasma alpha 1-ACT, were formed at the lower temperature whereas a single higher Mr band was formed when the samples were boiled. To determine whether cleavage of the serpin occurred, these studies were repeated using human neutrophil cathepsin G as target protease. A complex of approximately 90 kDa was formed with human alpha 1-ACT under these same conditions. alpha 1-ACT has been detected in senile amyloid plaques in brains of Alzheimer's disease patients, the only plasma serine protease inhibitor localized to these structures. Another serpin, protease nexin I, is also found in these plaques, but this inhibitor does not circulate in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of the serpin, alpha 1-antichymotrypsin, in normal human cerebrospinal fluid. 172 48

Using three antisera to oxytocin (OT Pitt Ab-1, OT Pitt Ab-2, and TOR OT Ab), we found comparable levels of OT in response to infant suckling and during infusion of synthetic OT, and identical standard curves with biological and synthetic standards of OT. Pitt Ab-1, but not Pitt Ab-2 or TOR OT Ab, measured increased OT in response to estrogen. Using an arginine vasotocin RIA (TOR AVT Ab), we found an increase in AVT immunoreactivity after estrogen treatment. Mean basal OT levels measured with OT Pitt Ab-2 in plasma of men [0.75 +/- 0.06 (+/- SEM) microU/ml] and women (0.8 +/- 0.09 microU/ml) were lower than OT measured with Pitt Ab-1 (1.7 +/- 0.09 microU/ml in men and 1.7 +/- 0.07 microU/al in women; P less than 0.001). Mean OT measured with Pitt Ab-2 in the plasma of women given estrogen chronically (0.8 +/- 0.04 microU/ml) and acutely (0.6 +/- 0.15 microU/ml) were not significantly different from basal levels. OT levels measured with Pitt Ab-1 in the same samples were 4.6 +/- 0.5 and 4.3 +/- 0.5 microU/ml, respectively, both significantly increased from basal levels (P less than 0.001) and significantly higher than OT measured with Pitt Ab-2 (P less than 0.001). Mean OT measured with Pitt Ab-1 in the plasma of pregnant women was 8.6 +/- 1.02 microU/ml, significantly higher than OT measured with Pitt Ab-2 (1.0 +/- 0.3 microU/ml; P less than 0.001). Men given 25 mg diethylstilbestrol had significant increases in OT measured with Pitt Ab-1 and in AVT measured with TOR AVT (P less than 0.01), but not in OT measured with Pitt Ab-2. Plasma from a man given diethylstilbestrol was prepared for high performance liquid chromatography and applied to a C18 muBondapak reverse phase column. The plasma contained two peaks of immunoreactivity detected as OT with Pitt Ab-1 and as AVT using TOR AVT Ab. The material was not detected by Pitt Ab-2 or TOR OT Ab and did not coelute with standards of OT, AVT, or AVP. Pregnancy plasma, thioglycolic acid, chymotrypsin, and trypsin reduced Pitt Ab-1, Pitt Ab-2, and TOR OT immunoreactivity of synthetic OT. The percent recovery of OT immunoreactivity was not significantly different with Pitt Ab-1 vs. Pitt Ab-2. A novel peptide, which is increased in response to administered estrogen, is present in human plasma and is detected by some antisera to OT and AVT. The observation explains the wide variability in OT levels in the estrogen-primed state and provides a new mechanism to study estrogen-related physiology and pathophysiology.
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PMID:A novel oxytocin-like and vasotocin-like peptide in human plasma after administration of estrogen. 396 93

We recently described a monoclonal antibody, 10E5 , that completely blocks adenosine diphosphate (ADP) induced fibrinogen binding to platelets and aggregation induced by ADP, epinephrine, and thrombin. Multiple lines of evidence indicate that 10E5 binds to platelet membrane glycoproteins IIb and/or IIIa. Because it has been reported that platelets treated with chymotrypsin aggregate when fibrinogen is added, we tested the effect of 10E5 antibody on chymotrypsin-induced fibrinogen binding and platelet aggregation. Aspirin-treated human platelets were washed in modified Tyrode's buffer (pH 7.5), incubated for 5 minutes at 22 degrees C with 300 micrograms/mL chymotrypsin, and washed again. The amount of 10E5 antibody bound to these platelets (37,232 +/- 2,928 molecules/platelet; mean +/- SEM, N=9) was similar to that bound to unstimulated control platelets (36,910 +/- 2,669) and did not differ significantly from the amount of antibody bound to ADP-treated platelets (P less than .01, N = 5). The amount of 10E5 bound to chymotrypsin-treated platelets correlated directly with the amount of fibrinogen bound to separate aliquots of the same platelet samples (r = .876, P less than .001). The 10E5 antibody caused virtually complete inhibition of both the binding of fibrinogen to chymotrypsin-treated platelets and the aggregation induced by exogenous fibrinogen. Immunoprecipitation studies of 125I-labeled chymotrypsin-treated platelets revealed that the 10E5 antibody bound proteins with molecular weights characteristic of glycoproteins IIb and IIIa. These data suggest that the fibrinogen receptor on chymotrypsin-treated platelets is identical to that on ADP-treated platelets and that this receptor is either near to, or on, the glycoprotein IIb/IIIa complex.
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PMID:A murine monoclonal antibody that blocks fibrinogen binding to normal platelets also inhibits fibrinogen interactions with chymotrypsin-treated platelets. 673 83

In fasting human serum, cholecystokinin (CCK) is not the principal substance which causes in vitro rabbit gallbladder contraction. Removal of CCK by affinity chromatography from fasting sera from 8 healthy adults reduced bioactivity only by 18 +/- 4% (SEM). Unlike CCK, the bioactivity of serum was enhanced by 30 to 57% rather than destroyed by pronase and chymotrypsin respectively and was not inhibited by dibutyryl cGMP. Reduction of serum bioactivity by carboxypeptidase Y indicated that the bioactive substances in serum are peptides. On Sephadex G-50, bioactive substances eluted in positions different from any known form of CCK. Thus, the principal substances in fasting human serum causing in vitro gallbladder contraction are not CCK but are most likely small peptides which act at receptors different from the receptors for CCK.
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PMID:Noncholecystokinin peptides in human serum which cause gallbladder contraction. 716 64

Because the terminal sialic acid of several glycoproteins regulates their intravascular half-life, and because asialo platelets have a shortened survival, we postulated that asialo platelets might affect the basal rate of thrombopoiesis. Thrombopoiesis was measured by the incorporation of intravenous 75Se-selenomethionine (a cohort label) into circulating rabbit platelets. Each animal acted as its own control. In one control group, saline was injected intravenously once daily for two days. 75Se-selenomethionine was then injected, 15 microCi/kgm on day 2 and platelets harvested on day 5 for measurement of specific activity (S.A.), cpm/10(7) platelets. The animals were allowed to rest for two weeks, and the experiment repeated. The ratio of the second SA over the first SA was utilized as the stimulation index. When saline was injected the second time, the stimulation index was 1.22 +/- 0.07 (SEM) in eight animals. Asialo platelets were prepared by incubating washed platelets with neuraminidase, 2 units/ml for 60 min. Injection of 2-4 X 10(9) asialo platelets/kgm (the second time) resulted in a stim. index of 2.08 +/- 0.23 (P less than 0.001) in 11 animals. Similar results were obtained with 1 mM DFP and neuraminidase (12 animals). Negative results were obtained when 11 rabbits were injected with a comparable number of untreated washed platelets, stim. index 1.07 +/- 0.13; when 10 rabbits were injected with sonicated asialo platelets, stim. index 1.10 +/- 0.12; or when four rabbits were injected with platelets treated with chymotrypsin, 3 mg/ml for 45 min, stim. index 0.80 +/- 0.04. We conclude that asialo intact platelets stimulate megakaryocytes to produce more platelets. It is suggested that the basal stimulus to thrombopoiesis may be regulated by desialidated older platelets.
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PMID:Asialo platelets enhance thrombopoiesis. 724 77

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

Plasma endothelin (ET) is increased in association with myocardial infarction. The aim of the present study was to get insight into the mechanisms behind this ischemia-induced increase in plasma ET. Since granulocytes increase ET production in vitro, we examined to what extent inhibition of granulocyte-derived proteases could reduce the increase in plasma ET observed in association with myocardial ischemia. We infused Eglin C, a selective inhibitor of the granulocyte-derived proteases elastase, cathepsin G, and chymotrypsin, in pigs subjected to 90 min left anterior descending coronary artery occlusion followed by 210 min reperfusion (n = 7). Arterial plasma ET increased in an untreated control group (n = 7) from 5.0 +/- 0.6 (mean +/- SEM) fmol . ml-1 before myocardial ischemia to 6.1 +/- 0.6 fmol . ml. at 90 min ischemia and reached a maximum of 6.8 +/- 0.9 fmol . ml-1 at 90 min reperfusion. The increase in plasma ET associated with myocardial ischemia was almost completely abolished in the Eglin C treated group (p = 0.005). Plasma ET in the Eglin C treated animals was 4.7 +/- 0.4, 4.7 +/- 0.4, and 4.6 +/- 0.4 fmol . ml-1 before myocardial ischemia, at 90 min ischemia, and at 90 min reperfusion, respectively. Our study suggests a role for granulocyte-derived proteases in the increase in plasma ET associated with myocardial ischemia. We have shown that the increase in plasma ET associated with myocardial ischemia was reduced by inhibition of granulocyte-derived proteases using the selective protease inhibitor Eglin C.
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PMID:Inhibition of granulocyte-derived proteases reduces the increase in plasma endothelin associated with myocardial ischemia in the pig. 887 78

We describe a tubeless test of exocrine pancreatic function based on a new dual isotope technique, using N-benzoyl-L-tyrosyl-p-aminobenzoic acid (NBT-PABA) as a substrate for intestinal chymotrypsin activity and the stable isotope, 13C-PABA as marker. Gas chromatography-mass spectrometry (GC-MS) was used for the quantification of PABA and 13C-PABA in blood. The method involves hydrolysis, extractions, separation by HPLC, and methyl ester formation of the test substances before GC-MS analysis. The test is precise and shows good separation of healthy volunteers from patients with pancreatic insufficiency. The PABA/13C-PABA ratios in serum after 1.5 h were 2.64 +/- 0.14 (mean +/- SEM) in 10 healthy volunteers and 1.26 +/- 0.22 in 10 patients with exocrine pancreatic insufficiency. We present a sensitive and specific assay, which is free of analytical interference and radiation hazards and, additionally, it illuminates extrapancreatic pharmacokinetic conditions. This test can eliminate the need for duodenal intubation, which makes it very acceptable to the patients.
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PMID:Determination of the exocrine pancreatic function with the NBT-PABA test using a novel dual isotope technique and gas chromatography-mass spectrometry. 920 Feb 75

The possible cardioprotective effects of preconditioning by ischaemia (IPC) or a low dose of H2O2 (HPC) prior to a high dose of H2O2 was investigated. Langendorff-perfused rat hearts (n = 10 in each group) were subjected to 10 min of 140 micromol/L H2O2 and 30 min recovery after either (1) control perfusion, (2) 20 micromol/L H2O2 for 10 min, recovery 10 min, or (3) 2 x 2 min global ischaemia and 5 min reperfusion. 140 micromol/L H2O2 increased left ventricular end-diastolic pressure from 0 to 68+/-8 mmHg in controls (mean+/-SEM), which was attenuated by IPC (46+/-9 mmHg, p<0.001) and HPC (18+/-4 mmHg, p < 0.001 compared to controls, p < 0.01 compared to IPC). HPC, but not IPC, improved coronary flow (p < 0.02) and left ventricular developed pressure (p < 0.001) during recovery. Troponin T release was similar in all groups. Tissue thiobarbituric acid reactive substances, antioxidant capacity, catalase, and glutathione peroxidase were not influenced by 140 micromol/L H2O2. H2O2 decreased the level of tissue glutathione. This reduction was augmented by HPC (p <0.02) and attenuated by IPC (p < 0.02). H2O2 increased superoxide dismutase (p < 0.04). The increase was attenuated by IPC (p < 0.05), but not influenced by HPC. HPC efficiently protected cardiac function in H2O2-induced cardiac injury, while IPC had only a small protective effect. The functional protection cannot be explained by reduction of irreversible injury, attenuation of lipid peroxidation, or modification of tissue antioxidant parameters.
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PMID:Preconditioning with hydrogen peroxide (H2O2) or ischemia in H2O2-induced cardiac dysfunction. 980 55

Tropical calcific pancreatitis (TCP) is a chronic, nonalcoholic pancreatitis, which is limited to developing countries. In this condition, surgical decompression of the pancreatic duct consistently leads to relief of abdominal pain. However, no data are available on the effect of such intervention on pancreatic function. The aim of the present study was to prospectively evaluate b-cell and exocrine function following ductal drainage in patients with TCP. We studied 14 consecutive TCP patients who underwent ductal decompression for abdominal pain (longitudinal pancreaticojejunostomyin 12 patients, endoscopic sphincterotomy and ductal stenting in 2 subjects). Six patients who refused similar intervention served as controls. Patients were evaluated prospectively (median follow-up 13 months) for pain score, fasting and oral glucose stimulated plasma C-peptide, serum trypsin, and fecal chymotrypsin. After intervention, 1 patient died 2 months after surgery, and 2 others were lost in follow-up. The pain score improved significantly following duct decompression (median 8.0 vs. 0, p < 0.01), while in the control group there was no change in pain score (7.0 vs. 7.0). There was no change in b-cell function after intervention (fasting plasma C-peptide [mean +/- SEM] 0.41 +/- 0.08 vs. 0.42 +/- 0.05 nmol/l; peak plasma C-peptide 2.24 +/- 0.20 vs. 2.32 +/- 0.24 nmol/l). Fecal chymotrypsin was diminished in all patients prior to intervention (1.9 +/- 0.7 U/g), and did not normalize after ductal drainage in any subject. Serum trypsin levels were variable, being elevated in 29% and diminished in 47% of subjects. All 4 subjects with elevated baseline trypsin levels had a sharp fall after intervention (1020 vs. 175 ng/ml). However, serum trypsin did not normalize after ductal drainage in any patient with a diminished baseline value. In conclusion, patients with TCP have significant reduction in abdominal pain after decompression of the main pancreatic duct. However, there is no significant change in b-cell function. A fall in elevated serum trypsin suggests that there may be relief of subclinical inflammation after intervention; however, there is no improvement in exocrine function after a follow-up of 1 year.
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PMID:Prospective study of pancreatic b-cell and exocrine function following duct decompression in tropical calcific pancreatitis. 1186 45


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