Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.4 (trypsin)
42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In untreated patients with inoperable lung cancer, serum levels of alpha1-antitrypsin were found significantly increased in comparison to patients with non malignant diseases of the lung, alpha2-macroglobulin levels were unchanged in both groups of patients. There was also no difference in alpha2-macroglobulins in cancer patients reacting with DNCB and in non-reactors. Thus alpha2-macroglobulin levels do not seem to correlate with the immunestatus of cancer patients. Proteinase inhibitors are involved in a variety of biological processes including blood, clotting, digestion, and sperm capacitation. alpha1-antitrypsin, a alpha-globulin with a molecular weight of about 60,000 has been found to be decreased in patients' serum under several pathological conditions. A clear correlation exists between alpha1-antitrypsin deficiency and hereditary pulmonary emphysema (1, 2), respiratory distress syndrome (3), and juvenile cirrhoses of the liver (4). Elevated serum levels of alpha1-antitrypsin have also been found in some cancer cases. Thirty years ago a cancer test was developed on the basis of differences in the antiproteolytic activity in cancer patients' sera and in patients with other non-neoplastic diseases (5, 6). Several authors have tried to confirm these early data regarding specifity and sensitivity with respect to a screening test for cancer (7, 8). Methods of these authors were based mainly on enzyme substrate inhibition assays by addition of the patients' sera. Recently a commercially available test, based on immune-precipitation according to Mancini (9), has been developed (Behring-Werke, Partigen). By using this standardized method for determinating alpha1-antitrypsin, Harris et al. have recently demonstrated that patients with inoperable lung cancer have significantly elevated levels of this antiprotease in their sera (10), in comparison to patients with non malignant diseases of the lung. alpha2-macroglobulin is a serum protein with a molecular weight of 800,000 and with known antiprotease activity and can therefore bind trypsin, plasmin, elastase, and collagenase and it is known that alpha2-macroglobulin decreases with increasing of age. Changes of alpha-macroglobulin have also been observed in several pathological conditions (11). James et al. 4ave found decreases in serum of myeloma patients (12). An association between the development and function of lymphocytes and alpha2-macroglobulin has been suggested by several authors (13, 14). This alpha2-globulin has also been demonstrated on the surface of peripheral blood lymphocytes (15) and there is evidence that it is synthesized by lymphocytes (16). The purpose of the present study was to determine serum alpha1-antitrypsin levels in patients with inoperable lung cancer and to determine whether there is also an inverse correlation to alpha2-macroglobulin. It was further attempted to correlate alpha2-macroglobulin with general immunological parameters, as it is known that patients with lung cancer show a decreased general immune-reactivity (17).
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PMID:Serum levels of alpha1-antitrypsin and alpha2-macroglobulin in lung cancer. 6 86

Exercise is a physical cause of allergic reactions, including exercise-induced anaphylaxis (EIAna), exercise-induced urticaria (EIU), exercise-induced asthma (EIA), and exercise-induced rhinitis (EIR). Since its first description in 1979, EIAna has been reported with variable clinical manifestations, with exercise alone, and in combination with food ingestion. Elevated serum histamine levels and cutaneous mast cell degranulation have been noted. Exercise-induced urticaria appears as small, punctate lesions that differ from the classic coalescent type seen with EIAna. Variant forms of EIAna with cholinergic urticarial lesions manifesting systemic collapse and/or respiratory distress have been studied. Exercise-induced urticaria and cold-induced urticaria may cause elevated plasma histamine levels coincident with the onset of pruritus and hives. Theories accounting for EIA include respiratory heat loss, water loss, and mast cell activation. Although some studies have shown increased plasma histamine with EIA, others have not. Recently, bronchoalveolar lavage in atopic subjects with EIA has been evaluated preexercise and postexercise, with no significant differences in histamine or tryptase, suggesting a pathogenesis of EIA independent of the mast cell. Exercise-induced rhinitis, with varying degrees of rhinorrhea, congestion, and sneezing, has been increasingly recognized in athletes who run, cycle, and ski. Cold-air-induced rhinorrhea in laboratory challenges displays a mediator release pattern similar to that produced by allergen-induced nasal challenges. Therapeutically, H1 antihistamines are recommended for EIAna both as pretreatment and acute therapy. H1 antihistamines may be helpful in EIU, but are recommended for EIAna both as pretreatment and acute therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Exercise-induced allergies: the role of histamine release. 137 Oct 41

Latex used in the manufacture of surgical gloves should be included in a list of allergens. It is found in the tree Hevea braziliensis. For approximately the last year, minutes after using surgical gloves, a female doctor had severe pruritus followed by a rash and angio-oedema of the contact areas. During the last 4 months, on opening the glove-bag, she experienced severe rhinitis and respiratory distress. The symptoms ceased in 1 h. Standard patch tests and with substances used in the manufacture of rubber were negative. Prick tests with glove and natural latex were strongly positive. The presence of specific IgE against natural latex was demonstrated by means of a histamine release assay as well as by immunoenzymatic methods. The antigen seems to have a MW higher than 30,000 d and is trypsin-sensitive. These facts suggest that the allergen could be a protein present in the "crude natural latex".
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PMID:Contact urticaria and rhinitis from latex surgical gloves. 243 Jul 55

In this experiment, rabbit model with smoke inhalation injury was used. The study was designed to observe the dynamic changes of elastase activities of polymorphonuclear leukocytes (PMN), alveolar macrophages (AM) and bronchoalveolar lavage fluid (BALF); and trypsin inhibitory capacities of serum and BALF (STIC & BTIC). The relationships between these changes and acute lung injury, as well as the concomitant changes of arterial blood gas levels, lung water volume and pathomorphology of trachea and lung tissues were also observed. It was found that after injury the elastase activities of PMN and AM were markedly reduced, and the elastase activity of BALF was rapidly increased. STIC was also reduced. PaO2 progressively dropped and PaCO2 progressively increased. Animals showed respiratory distress. Pathomorphological phagocytes aggregations in lungs, pulmonary edema and pneumorrhagia were found. There were serious destructions of capillary endothelial cells, alveolar epithelial cells, basement membranes and interstitial fibers. The number of elastic fibers of parenchyma decreased. The lung water volume was markedly increased, and there was a significant correlation between the increment of extravascular lung water and the rising of elastase activity of BALF. On the basis of our observation, it is proposed that the imbalance of elastase-antiprotease may play an important role in the development of acute lung injury after smoke inhalation.
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PMID:[Experimental study of dynamic changes in elastase-antiprotease in rabbits in the early stage of inhalation injury]. 251 41

Oxidant injury and release of proteolytic enzymes in prematures with respiratory distress syndrome (RDS), who are treated with ventilators and oxygen, have been postulated as possible causes of bronchopulmonary dysplasia (BPD). The premature may be at particular risk due to low levels of antiproteases, such as alpha-1-proteinase inhibitor (alpha 1PI), and antioxidants, such as ceruloplasmin (CER). Both alpha 1PI and CER deficiencies have been correlated with the severity of RDS. We studied serial alpha 1PI activity as measured by trypsin inhibitory capacity (TIC) and CER in the serum 27 prematures who required ventilator therapy for RDS. Serum TIC values for day 1 were significantly lower (0.34 vs. 0.92 mg inhibited/ml of sample) in the 13 patients who developed BPD compared to the 14 who did not. No significant differences were seen on succeeding days. No significant differences in CER were seen, although both groups had levels 33-50% of adult normals (11.3 vs 9.3 mg/dl). Other significant variables included birthweight (p less than 0.005), severity of RDS (p less than 0.03), and gestational age (p less than 0.03). One way analysis of variances demonstrated day 1 TIC to be the most significant variable (p less than 0.0001), followed by weight (p less than 0.007), severity RDS (p less than 0.04), and gestational age (p less than 0.03). CER levels were not a significant variable. A formula utilizing unstandardized canonical discriminant function including day 1 TIC, birthweight, severity of RDS, and gestational age was 100% sensitive and 85% specific in the prediction of BPD for the original study group. In an additional 25 consecutive admissions with severe RDS of whom 18 survived, the formula was 100% sensitive (6/6) and 75% specific (9/12).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serial trypsin inhibitory capacity and ceruloplasmin levels in prematures at risk for bronchopulmonary dysplasia. 349 55

A 38-year-old woman was admitted for intranasal ethmoidectomy. She had a history of serious anaphylactic reactions, including respiratory distress, hypotension and unconsciousness, to nonsteroidal anti-inflammatory drugs (Loxonin, Niflan) and antibiotics (Kefral, Minomycin). Preoperative intradermal skin tests against anesthesia-related drugs showed positive reactions to succinylcholine and vecuronium. After bilateral maxillary nerve block with 0.5 % bupivacaine (negative intradermal test) 3 ml, anesthesia was induced with diazepam, nitrous oxide, oxygen and sevoflurane. Trachea was intubated smoothly without muscle relaxants. Anesthesia was maintained with nitrous oxide, oxygen and sevoflurane 0.5-1 %. The anesthesia and postoperative course of this patient were uneventful. To confirm the initiation of allergic reaction to anesthetics used in the patient, serum histamine, tryptase, and complement 1, 3 and 4 factors were measured at 3 points: preoperatively, immediately after the induction, and after extubation. They showed normal levels. These results showed that no allergic reaction occurred perioperatively. In conclusion, the valuable information was provided for the choice of anesthetics by thorough evaluation of the past history and intradermal testing.
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PMID:[Anesthesia in a patient with history of multiple drug allergies]. 854 94

An inhibitor of alpha-thrombin was designed on the basis of the X-ray crystal structures of thrombin and trypsin. The design strategy employed the geometric and electrostatic differences between the specificity pockets of the two enzymes. These differences arise due to the replacement of Ser 190 in trypsin by Ala 190 in thrombin. The new inhibitor contained a tryptophan side chain instead of the arginine side chain that is present in the prototypical thrombin inhibitors. This inhibitor had a Ki value of 0.25 microM, displayed more than 400-fold specificity for thrombin over trypsin, and doubled the rat plasma APTT at a concentration of 44.9 microM. The X-ray crystal structure of the inhibitor/alpha-thrombin complex was determined. This represents the first reported three-dimensional structure of a thrombin/ inhibitor complex where the specificity pocket of the enzyme is occupied by a chemical moiety other than a guanidino or an amidino group. As was predicted by the molecular model, the tryptophan side chain docks into the specificity pocket of the enzyme. This finding is in contrast with the indole binding region of thrombin reported earlier [Berliner, L. J., & Shen, Y. Y. L. (1977) Biochemistry 16, 4622-4626]. The lower binding affinity of the new inhibitor for trypsin, compared to that for thrombin, appears to be due to (i) the extra energy required to deform the smaller specificity pocket of trypsin to accommodate the bulky indole group and (ii) the favorable electrostatic interactions of the indole group with the more hydrophobic specificity pocket of thrombin. The neutral indole group may be of pharmacological significance because the severe hypotension and respiratory distress observed following the administration of some thrombin inhibitors have been linked to the positively charged guanidino or amidino functionalities.
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PMID:Molecular design and characterization of an alpha-thrombin inhibitor containing a novel P1 moiety. 903 93

Microvascular endothelial cells (MVEC), which differ from large vessel endothelial cells, have been isolated successfully from lungs of various species, including man. However, contamination by nonendothelial cells remains a major problem in spite of several technical improvements. In view of the organ specificity of MVEC, endothelial cells should be derived from the tissue involved in the diseases one wishes to study. Therefore, to investigate some of the immunopathological mechanisms leading to acute respiratory distress syndrome (ARDS), we have attempted to isolate lung MVEC from patients undergoing thoracic surgery for lung carcinoma and patients dying of ARDS. The method described here includes four main steps: (1) full digestion of pulmonary tissue with trypsin and collagenase, (2) aggregation of MVEC induced by human plasma, (3) Percoll density centrifugation, and (4) selection and transfer of MVEC after local digestion with trypsin/EDTA under light microscopy. Normal and ARDS-derived lung MVEC purified by this technique presented contact inhibition (i.e., grew in monolayer), and expressed classical endothelial markers, including von Willebrand factor (vWF), platelet endothelial cell adhesion molecule 1(PECAM-1, CD31), and transcripts for the angiotensin converting enzyme (ACE). The cells also formed capillarylike structures, took up high levels of acetylated low-density lipoprotein (Ac-LDL), and exhibited ELAM-1 inducibility in response to TNF. Contaminant cells, such as fibroblasts, smooth muscle cells, or pericytes, were easily recognized on the basis of morphology and were eliminated by selection of plasma-aggregated cells under light microscopy. The technique presented here allows one to study the specific involvement and contribution of pulmonary endothelium in various lung diseases.
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PMID:An improved method for isolation of microvascular endothelial cells from normal and inflamed human lung. 971 12

Cystic fibrosis is the most common life-limiting recessive genetic disorder in Caucasian. It is caused by mutations of CFTR gene (cystic fibrosis transmembrane conductance regulator); at present over 500 mutations are known. Cystic fibrosis as a cause of respiratory distress in the neonate is quite rare. In neonatal period the most important clinical manifestations are meconium ileum and much rarely cholestatic jaundice. We present two cases of cystic fibrosis in newborns. In the first one, we point out the strict association between meconium ileum and cystic fibrosis. The patient underwent a surgical treatment for meconium ileum and the diagnosis was rapidly confirmed by genetic analysis and sweat test. The second one had intestinal obstruction from birth caused by meconium ileum associated with ileal atresia; besides, he developed cholestatic jaundice, severe and rapidly progressive respiratory disease. He died at 102 degrees day of age for cardiac failure. The diagnosis of cystic fibrosis, supported by typical clinical features and high level of serum trypsin, unfortunately wasn't confirmed by genetic analysis (lambda F508/neg), in addition, the sweat test wasn't reliable because an inadequate quantity of sweat was collected.
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PMID:[Neonatal cystic fibrosis: report of 2 cases]. 1142 48

Children who are destined to develop asthma are considered to be susceptible to a variety of respiratory pathogens. To elucidate respiratory inflammation among these children, we measured the levels of eosinophil cationic protein (ECP) and tryptase in sputum taken from three different groups of wheezy infants and young children: those with a first wheeze (n = 15); those with recurrent wheeze (n = 27); and those with recurrent wheeze with respiratory distress, namely asthma (n = 56). The numbers of eosinophils or metachromatic cells determined by microscopic analysis of sputum samples were also evaluated in combination with the ECP and tryptase levels. Although neither sputum ECP nor tryptase was a clear discriminative marker that differentiated the three different types of wheezy disease, ECP levels in sputum from the asthma group were significantly higher (2,269.2 +/- 6,216.8 ng/g) than those in the recurrent wheezy group (440.3 +/- 1,199.8 ng/g) or in the first-wheeze group (209.0 +/- 172.9 ng/g). A similar trend was observed with tryptase levels in sputum, but there were no significant differences among the three groups. Sputum taken from asthmatic children showed a marked accumulation of eosinophils. However, an accumulation of eosinophils in sputum (even in the presence of an elevated level of sputum ECP) was not identified in the asthmatic infants < 1 year of age. An accumlation of eosinophils in sputum was not evident until children became > 1 year old and thereafter the eosinophils rapidly increased in number until the children reached 5 years of age. It was noteworthy that sputa positive for pathogenic bacteria, taken from the 1- and 2-year-old asthmatic infants, had a tendency to show high levels of ECP but a reduced number of eosinophils. Along with the wheezy episodes induced by viral infection, primarily and occasionally in combination with secondary bacterial infection, eosinophil activation and infiltration may develop. These predestined immune reactions to various pathogens might be associated with triggering the onset of asthma.
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PMID:Analysis of sputum taken from wheezy and asthmatic infants and children, with special reference to respiratory infections. 1184 69


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