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)

Ocular allergic diseases are characterized by specific activation of conjunctival mast cells with subsequent release of preformed and newly formed mediators. Mast-cell numbers on the ocular surface are increased in all forms of allergic conjunctivitis. Mast-cell activation plays a central role in the development of the ocular allergic reaction, which can be divided into an early and a late inflammatory phase. Mast-cell mediators have been measured in tears of patients suffering from various forms of allergic conjunctivitis, and in sensitized patients after specific ocular allergen challenge. Histamine and tryptase are the most studied mediators in tears of allergic patients. Several cytokines, such as IL-4 and TNF-a, are also produced and released by conjunctival mast cells, and probably play a role in the immunoregulation on the ocular surface. In vitro studies of the characteristics and biologic functions of conjunctival mast cells highlight their central role in the pathogenesis of ocular allergy, and have led to new opportunities to evaluate anti-allergic compounds. This review discusses the role of conjunctival mast cells in the development of ocular allergic diseases.
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PMID:The central role of conjunctival mast cells in the pathogenesis of ocular allergy. 1204 69

Varicose veins of the lower extremities are abnormally dilated, tortuous and elongated. The exact cause of vein dilatation has still not been established. Mast cells produce, store and release various types of vasoactive compounds (histamine, tryptase, prostaglandins, leukotrienes, and cytokines). Histamine enhances local vasopermeability and smooth muscle cell proliferation, leading to thickening of the intima. Tryptase can contribute to local vascular injury and subsequent weakness of the vascular wall causing varix formation. The aim of the present study was the comparison of mast cell infiltration in the wall of varicose and non-varicose veins. The mean mast cell density in the wall of varicose veins was 0.86 mast cell per mm2 and in healthy non-dilated vein walls, density was 1.23 mast cell per mm2. This difference was not statistically significant, therefore we could not confirm our hypothesis. Nevertheless, we suggest that mast cells could play an important role in the development of varices and the factor released by the mast cells should be further examined.
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PMID:Mast cell infiltration in the wall of varicose veins. 1255 2

Mast cells accumulate and persist predominantly in the upper dermis of the skin but the mechanism for this is obscure. The skin is normally exposed to external air, which is essential for the maturation of the epidermis and probably also the dermis. In order to clarify the importance of air exposure on dermal mast cells, skin organ culture at the air-liquid interface (ALI) and submerged (SM) in medium (10% fetal calf serum and Dulbecco's modification of Eagle's medium) was used to study changes in tryptase-, chymase- and Kit-positive mast cell numbers during cultivation for up to 14 days. In addition, possible apoptosis (TACS TdT in situ apoptosis detection method) in chymase-positive mast cells was studied during the culture. In the less-physiologic SM culture, the number of Kit-positive mast cells decreased rapidly on day 1-2 and tryptase-positive cells decreased markedly on day 14. This decrease in mast cell numbers can be explained by the finding that a rapid increase in the apoptosis index of mast cells was induced on day 1-2. In contrast, in the more physiologic ALI culture, the number of Kit-positive cells was sustained over 1-2 days but then decreased on day 7. In addition, tryptase-positive cells decreased steadily in number but not to the same extent as those in the SM culture. Moreover, the increase in the apoptosis index of mast cells was delayed until day 7 in the ALI culture. Addition of exogenous stem cell factor (up to 200 ng/ml) to the SM culture could not prevent the decay in tryptase- and chymase-positive cells. However, stem cell factor reduced significantly the number of Kit-positive cells already on day 2 indicating that the cells had responded. Addition of histamine (0.25 or 1 mM) or tumor necrosis factor-alpha (500 or 2000 U/ml) caused a decrease in the number of tryptase- and Kit-positive cells in the SM culture. In conclusion, a novel finding was that air exposure in the ALI culture markedly delayed the rapid apoptosis and subsequent decrease in mast cell numbers noted to occur in the SM culture. Stem cell factor could not prevent the rapid decrease in mast cell numbers. Histamine and tumor necrosis factor-alpha are possible factors promoting the decline in mast cells.
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PMID:Mast cell survival and apoptosis in organ-cultured human skin. 1263 Dec 47

Methylprednisolone sodium succinate (MPS) is widely used in the management of renal transplantation. Of interest is the rare occurrence of anaphylaxis and anaphylactoid reaction to MPS. We report on a patient who developed anaphylaxis following the intravenous administration of MPS during a renal transplant operation. Intracutaneous testing was carried out with MPS and a strong positive reaction was observed. Histamine and tryptase concentrations were high after the anaphylactic reaction. Including the present case, there have been 13 reports of anaphylactic or anaphylactoid reactions to MPS, occurring in renal transplant recipients. Clinicians should be aware of the potential risk of MPS administration. If transplant patients undergo skin testing against MPS prior to transplant, they may benefit from an alternative medication with other corticosteroids. To use MPS without severe adverse reactions, lower administration rates and dosages are very important.
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PMID:Anaphylaxis following administration of intravenous methylprednisolone sodium succinate in a renal transplant recipient. 1500 66

Mast cells are able to induce proliferation of skin fibroblasts; however, their effect on lung fibroblasts has not been clearly established. Using in vitro cocultures of rat or human mast cells with lung fibroblasts, the authors determined whether mast cells alter proliferation, collagen synthesis, and metalloproteinase production from lung fibroblasts. Mast cells enhanced the proliferation of human fibroblasts (mean +/- SEM: 90% +/- 4.7% increase, P < .001) while inhibiting fibroblast collagen synthesis (48.1% +/- 4.2% decrease, P < .001). Histamine, but not tryptase, significantly enhanced fibroblast proliferation: 92% +/- 5.8% (P < .001) and 39.2% +/- 4.3% (P > 0.05), respectively. Rat mast cell sonicate added to lung fibroblasts induced the activation of metalloproteinase-9 while inhibiting that of metaloproteinase-2. The addition of lipopolysaccharide (LPS)-stimulated lung macrophage supernatant further enhanced the poliferative effect of mast cells on fibroblasts (by 60% +/- 7.8%, P < .001) and induced synthesis of collagen from these cells (190% +/- 28% increase versus control, P < .05). This study demonstrates that mast cells influence several aspects of lung fibroblast function in vitro.
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PMID:Mast cells induce activation of human lung fibroblasts in vitro. 1570 May 48

Histamine, an inflammatory mediator in its own right, may also be a marker for a more widespread systemic inflammatory process. In this study we have examined variations in plasma histamine concentrations produced during the course of cardiac surgery involving cardiopulmonary bypass, the relationship between these variations and intra-operative events. By assays of serum tryptase and CD-63 expression we have also attempted to identify the source of histamine. Histamine concentrations that were significantly raised from baseline level were demonstrated. These were elevated from the time of aortic cross-clamping and continued to be raised for 24 h postoperatively (p < 0.00625). This was associated with an increase in CD-63 expression (p < 0.025) (but not an increase in tryptase concentration) following aortic cross-clamping and protamine administration, suggesting that basophils are the source of histamine. 41% of patients had arrhythmias in the post bypass period. The rise in histamine levels was not related to the incidence of cardiac arrhythmias.
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PMID:Histamine release during adult cardiopulmonary bypass. 1628 15

Histamine is an important mediator of allergic responses. Arthropods express several biologically active proteins in their saliva, which may allow a prolonged blood meal on the host. Proteins identified and expressed include histamine, serotonin, tryptase, and complement binding proteins. We review here data that scavenging of endogenous histamine by the histamine-binding protein EV131 has a profound inhibitory effect on allergic asthma. Aerosol administration of EV131 prevented airway hyperreactivity and abrogated peribronchial inflammation, eosinophil recruitment, mucus hypersecretion, and IL-4 and IL-5 secretion. Saturation with histamine abrogated the inhibitory effect of EV131 on bronchial hyperreactivity. The data suggest that histamine plays a role in allergies and that scavenging of histamine by EV131 may represent a novel therapeutic strategy in the treatment of allergic diseases.
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PMID:Arthropod-derived protein EV131 inhibits histamine action and allergic asthma. 1638 87

Disorders of mast cells, particularly mast cell tumors (MCTs), are common in dogs. There now is evidence that many of these disorders exhibit breed predilections, suggesting an underlying heritable component. In comparison to humans and mice, little is known regarding the biology of canine mast cells. To facilitate the study of mast cell biology in other species, bone marrow-derived cultured mast cells (BMCMCs) often are used because these represent a ready source of large numbers of cells. We have developed a protocol to successfully generate canine BMCMCs from purified CD34(+) cells. After 5-7 weeks of culture with recombinant canine stem cell factor (rcSCF), greater than 90% of the cell population consisted of mast cells as evidenced by staining with Wright's-Giemsa, as well as production of chymase, tryptase, IL-8 and MCP-1. These cells expressed cell surface markers typical of mast cells including Kit, Fc epsilonRI, CD44, CD45 and CD18/CD11b. The canine BMCMCs were dependent on rcSCF for survival and proliferation, and migrated in response to rcSCF gradients. Cross-linking of cell surface-bound IgE induced the release of histamine and TNFalpha. Histamine release could also be stimulated by ConA, compound 48/80, and calcium ionophore. In summary, canine BMCMCs possess phenotypic and functional properties similar to mast cells found in vivo. These cells represent a novel, valuable resource for investigating normal canine mast cell biology as well as for identifying factors that lead to mast cell dysregulation in the dog.
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PMID:Generation and characterization of bone marrow-derived cultured canine mast cells. 1678 Sep 61

Medullary thyroid cancer (MTC) shares biochemical features with other neuroendocrine tumors but the particular characteristics are largely unexplored. We investigated the biochemical neuroendocrine profile of MTC and whether specific markers could be useful in follow-up. In addition to the standard tumor marker calcitonin, plasma carcino-embryonic antigen (CEA), plasma catecholamines, (platelet) serotonin, chromogranin A, tryptase, and urinary markers of catecholamine, histamine, and serotonin metabolism were prospectively determined in 46 patients with histologically proven MTC. Patients were divided according to the stage of disease: group 1, no evidence; group 2, stable disease (SD); and group 3, progressive disease (PD). Plasma dopamine was increased in the majority of the patients with SD and PD; however it did not correlate with extent of disease. Elevated plasma platelet levels of serotonin were only present in patients with multiple endocrine neoplasia 2 with SD or PD but did not differ between those groups. Histamine metabolites were elevated in 20% of patients with SD and PD. In addition to plasma calcitonin, only CEA and chromogranin A could differentiate between stable and progressive MTC. MTCs are capable of synthesizing catecholamines, serotonin, and histamine metabolites underscoring that MTCs have metabolic characteristics in common with other neuroendocrine tumors. Thus far, clinical usefulness and relevance seems limited. The most useful markers in the follow-up of MTC are plasma calcitonin and CEA.
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PMID:Biochemical markers in the follow-up of medullary thyroid cancer. 1712 44

In this prospective study, a quantitative determination of histamine and tryptase in nasal secretions after nasal phosphate buffered saline (PBS) and allergen challenge was performed in 18 atopic patients who were compared with ten non-allergic healthy volunteers. The aim of the study was to determine the normal and pathological concentrations of these important mediators in nasal secretions. The second objective was to test the relevance of these two mast cell secreted mediators after nasal challenge. Results showed that the concentrations of tryptase in almost all samples were under the minimal detection limit (< 0.5 muU/g) and only a sigrtificant increase of tryptase (median, 28 muU/g) occurred immediately after nasal allergen challenge in the patient group. Histamine concentration significantly increased after every nasal PBS challenge (median, 69 ng/g after first PBS challenge and 165 ng/g after second PBS challenge) in the control group, as well as in the patient group after both PBS (median, 69 ng/g) and allergen (median, 214 ng/g) challenge. On the other hand, a rapid onset of sneezing and increase in nasal airway resistance was experienced only in the patient group after nasal allergen challenge, but did not occur after PBS challenge even though the histamine concentrations significantly increased in both groups. This study suggests that tryptase is a more preferable marker than histamine in quantitative monitoring of mast cell activation especially during the early phase nasal allergic reaction.
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PMID:Relevance of histamine and tryptase concentrations in nasal secretions after nasal challenges with phosphate buffered saline and allergen. 1847 23


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