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)

The accumulation of the large and hydrophilic IgG, TC II-B12 and B12 molecules is demonstrated for the first time in a human placental system which has metabolic and physiological functions. A trypsin-sensitive component is present in the human term placental uptake of TC II-B12, for which a placental membrane receptor has been previously identified; this component is absent for the accumulation of free B12, which has no known receptor. Analyses of the cytosol and incubation media indicate degradation, binding and release of TC II-B12 and B12 as TC II-B12, free B12 and TC I-like complexes. It is suggested that the human placental tissue slice be used for studies involving the binding, uptake and processing of macromolecules as exemplified by TC II-B12.
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PMID:Macromolecule transfer in the human trophoblast: transcobalamin II-vitamin B12 uptake. 696 54

Trypsin inhibited 57CoB12-rat IF uptake by rat small intestinal mucosa homogenates in vitro. This tryptic inhibition was inactivated by rat serum and normal human serum, as well as soybean trypsin inhibitor (STI). The effects of trypsin dissolved in distilled water or 0.0025 N HCl, 0.15 M saline extract of rat pancreas and STI on vitamin B12 absorption were studied in vivo, using gastrectomized rats. IF-mediated B12 absorption was significantly decreased by 5 mg of trypsin dissolved either in distilled water or 0.0025 N HCl. However, the inhibition of trypsin was much more remarkable when it was dissolved in 0.0025 N HCl, whereas B12 absorption was insignificantly decreased by administering 10 mg of trypsin dissolved in 0.0025 N HCl. The possibilities of this phenomenon was discussed. The inhibitory effect of 0.5 ml of 0.15 M saline extract of rat pancreas was investigated as well. Soybean trypsin inhibition showed no effect on B12 absorption when it was given with 57CoB12-rat IF at the same time. However, the B12 absorption was significantly increased when STI was given one hour prior to the administration of 57CoB12-rat IF. This suggested that endogenous trypsin bound to rat small intestine had been inactivated and pancreatic secretion had been stimulated by STI. IF-mediated B12 absorption was diminished to almost the same level of 57CoB12 administration alone by simultaneous intubation of both 57CoB12-rat IF and rabbit anti-rat IF serum in total gastrectomized rats.
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PMID:Effects of proteolytic enzymes on vitamin B12 uptake by rat intestinal mucosa homogenates and of proteolytic enzymes and anti-rat intrinsic factor antibodies on vitamin B12 absorption in total gastrectomized rats. 702 41

A thymic epithelial cell line Mm2T was cultured in a medium containing a high concentration (100 micrograms/ml) of methylated vitamin B12 (CH3-B12). After 19 days, cells were found to have a flat phenotype, to have lost the floating cells which were observed in the control cells at the confluent stage, and to have acquired a resistance to trypsin. However, treatment of the CH3-B12-treated cells with EDTA resulted in a dissociation of cell-to-cell contact and reaggregation was achieved by addition of Ca2+, indicating the involvement of Ca2+ ion in cell-to-cell contact. Electron microscopic analyses revealed that the CH3-B12-treated cells were nearly square in their vertical section, which was in contrast to the dome-shaped feature of the control cells, and their cell-to-cell contact area was significantly widespread, as compared to those of the control, indicating that Mm2T cells acquires an adhesive property by treatment with CH3-B12. Biochemical analyses of both cells indicated that the concentration of glucosylceramide in the CH3-B12-treated cells was higher than that of the control. Free glucose characteristically inhibited the reattachment of cells dissociated with EDTA, suggesting the involvement of glucose in the cell-to-cell adhesion of CH3-B12-treated cells. In addition, WGA-binding glycoconjugates were intensely observed in the boundary region of CH3-B12-treated cells by immunohistochemical staining, but not in that of the control cells. It is suggested that CH3-B12 may affect the morphological alteration of Mm2T by enhancing cell adhesion through elevated expression of the C-type lectin.
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PMID:Enhancement of adhesive property of epithelial cell line Mm2T by culture in the presence of methylated vitamin B12. 758 11

Tryptase, a neutral protease, is selectively concentrated in the secretory granules of human mast cells, and its release into the circulation serves as a clinical marker of mast cell activation. The current study describes a new, more sensitive ELISA utilizing a newly developed, mouse monoclonal IgG1 antibody for capture called B12 and capable of detecting tryptase in normal plasma and serum. The greater sensitivity of the new immunoassay results in part from a greater portion of tryptase being detected. Mean levels of tryptase in serum from normal subjects from Richmond, Virginia (4.9 ng/ml; n = 56), Munich, Germany (3.8 ng/ml; n = 19), and Amersfoort, The Netherlands (1.9 ng/ml; n = 8) were as indicated. In 62 subjects with ongoing allergic rhinitis, tryptase levels were no different in serum than for 19 normal controls, indicating that local mast cell activation is not necessarily reflected in the circulation. In 61 subjects sensitive to honey bee or yellow jacket venom by history, the 17 destined to have a severe, hypotensive response to a sting challenge had higher levels of tryptase at baseline than mild reactors, nonreactors, and controls, suggesting that baseline levels of tryptase may predict the severity of the clinical response to allergen in sensitive subjects.
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PMID:Development of a new, more sensitive immunoassay for human tryptase: use in systemic anaphylaxis. 792 94

Here we report the occurrence of five different beta chain hemoglobin variants not previously described in Sweden. The variants were found during quantification of HbA1c using ion exchange high performance liquid chromatography (HPLC) or isoelectrofocusing. Samples were examined either at protein level by separation of globin chains on C8 reversed phase HPLC, digestion with trypsin or lysylendopeptidase and separation of peptides by C18 reversed phase HPLC, or at DNA level by direct nucleotide sequencing of double-stranded DNA fragments amplified from exon 1 + 2 of the beta-globin gene. The variants were: Hb Raleigh [beta 1 (NA1)Val-->Ac-Ala], Hb J-Baltimore [beta 16(A13)Gly-->Asp], Hb Tacoma [beta 30(B12)Arg-->Ser], Hb K-Ibadan [beta 46(CD5)Gly-->Glu], and Hb Fukuyama [beta 77(EF1)His-->Tyr]. Hb Tacoma, Hb K-Ibadan, and Hb Fukuyama were slightly unstable in the isopropanol test, but no signs of hemolysis were found in the patients who all had normal hematological findings.
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PMID:Rare beta chain hemoglobin variants found in Swedish patients during HBA1c analysis. 822 93

Tryptase, a protease produced by all mast cells, was evaluated as a clinical marker of systemic mastocytosis. Two sandwich immunoassays were evaluated, one which used the mAb G5 for capture, the other which used B12 for capture. The B12 capture assay measured both recombinant alpha- and beta-tryptase, whereas the G5 capture assay measured primarily recombinant beta-tryptase. G5 binds with low affinity to both recombinant alpha-tryptase and tryptase in blood from normal and nonacute mastocytosis subjects, and binds with high affinity to recombinant beta-tryptase, tryptase in serum during anaphylaxis, and tryptase stored in mast cell secretory granules. B12 recognizes all of these forms of tryptase with high affinity. As reported previously, during systemic anaphylaxis in patients without known mastocytosis, the ratio of B12- to G5-measured tryptase was always < 5 and approached unity (Schwartz L.B., T.R. Bradford, C. Rouse, A.-M. Irani, G. Rasp, J.K. Van der Zwan and P.-W.G. Van der Linden, J. Clin. Immunol. 14:190-204). In this report, most mastocytosis patients with systemic disease have B12-measured tryptase levels that are elevated (> 20 ng/ml) and are at least 10-fold greater than the corresponding G5-measured tryptase level. Most of those subjects with B12-measured tryptase levels of < 20 ng/ml had only cutaneous manifestations. The B12 assay for alpha-tryptase and beta-tryptase, particularly when performed in conjunction with the G5 assay for beta-tryptase, provides a more precise measure of mast cell involvement than currently available assessments, a promising potential screening test for systemic mastocytosis and may provide an improved means to follow disease progression and response to therapy.
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PMID:The alpha form of human tryptase is the predominant type present in blood at baseline in normal subjects and is elevated in those with systemic mastocytosis. 867 37

Human tryptase is uniquely regulated by its association with heparin and resists inhibition by biological protease inhibitors. The effects of pH and B12, an IgG anti-tryptase mAb, on cleavage of the synthetic substrate tosyl-Gly-Pro-Lys-p-nitroanilide and of the biological substrate fibrinogen by tryptase were examined. Tosyl-Gly-Pro-Lys-pnitroanilide cleavage was optimal at neutral pH and was inhibited by the B12 mAb at acidic and neutral pH values. At pH 7.5, inhibition was reversible and noncompetitive. In contrast, the optimal pH for tryptase to cleave fibrinogen was acidic. B12 dramatically enhanced the rate and extent that tryptase cleaved all three fibrinogen subunits at pH 6.0 to 6.5, but inhibited these activities at neutral pH. Major fibrinogen cleavage fragments generated at acidic pH by the B12:tryptase complex were identical with those made by plasmin. Thus, at acid pH, tryptase alone destroyed the ability of fibrinogen to clot, while the B12:tryptase complex increased the rate of fibrinogenolysis and also generated the anticoagulant, fragment D. The acidic pH optimum for tryptase fibrinogenolysis may direct this activity to tissue sites of inflammation. A putative biological equivalent to B12 would limit tryptase fibrinogenolytic activity at sites of neutral pH, such as blood, but would augment activity at acidic sites.
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PMID:Human tryptase fibrinogenolysis is optimal at acidic pH and generates anticoagulant fragments in the presence of the anti-tryptase monoclonal antibody B12. 931 53

Serum tryptase was measured with the B12 and G5 antibody-based immunoassays in 25 adult patients with mastocytosis and in 18 controls. Twelve patients had uncomplicated cutaneous mastocytosis (urticaria pigmentosa) and 13 had urticaria pigmentosa with systemic symptoms. Tryptase levels were compared with histamine turnover estimated as urinary excretion of the main histamine metabolite tele-methylimidazoleacetic acid. Elevated B12 tryptase levels (> 20 microg/L) were found in most mastocytosis patients, including five of eight patients with only cutaneous manifestations who had a low urinary histamine metabolite excretion. This indicated a higher sensitivity for diagnosing mild mastocytosis on the basis of levels of serum tryptase as opposed to urinary methylimidazoleacetic acid. However, the serum B12 tryptase assay could not differentiate between urticaria pigmentosa patients with and without systemic disease: the measurement of histamine metabolite excretion probably reflects the mast cell burden more accurately. Serum G5 tryptase levels were generally low in both controls and mastocytosis patients.
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PMID:Serum tryptase measured with B12 and G5 antibody-based immunoassays in mastocytosis patients and its relation to histamine turnover. 989 55

Malignancies are common in the digestive tube, although with unequal distribution among segments. The aim of this paper was to compare available interpretations of the low cancer incidence in the small bowel and high in the large bowel. Supposed mechanisms include relatively small bacterial population, large secretion of liquid and rapid transit in the small bowel. Small bowel mucosa is the main absorptive part of the digestive tube with absorption rates for various nutrients so high that they can even be considered as clearances from the intestinal content. Consequently, these nutrients are not present in the large bowel. An alternative explanation is that an absorbable protective substance from the intraluminal content, might protect the mucosa from malignant transformations. It can be speculated that if there are any cytoprotective substances in the digested food their effect would be expressed mostly in the absorptive small intestine, leaving the large bowel mucosa unprotected. Vitamin B12 might be a possible candidate for this role. Cobalamin molecules are initially bound to haptocorrin (Hc) in the stomach, but in the small intestine B12 is transferred to intrinsic factor (IF) after the action of pancreatic trypsin on Hc. Cobalamin-IF complexes are absorbed in the terminal ileum leaving only a small fraction of B12 to enter the large bowel. We have tried to summarize available data regarding cancer incidences in digestive tube, segmental length and transit times of tube content. Cancer density is calculated as incidence per length and transit speed as length per transit time. Cancer incidences for seven intestinal segments were considered low if they were below one case per 100 000 inhabitants annually, while the low cancer density meant less than six cases per 100 000 inhabitants per metre. For instance, transverse colon was considered as a high cancer incidence place (2.15 cases), with low cancer density (4.3 cases/m). Transit speed more than 0.3 metre/hour was associated with low cancer incidences (accuracy 0.85) and low cancer density segments (accuracy 1.00). Cobalamin availability showed similar distribution, available in low incidence segments and unavailable in high incidence segments. Experimental studies are needed to quantify B12 availability in the large bowel and to determine whether small amounts of B12-IF or, perhaps, B12-haptocorrin complexes are absorbed by the small bowel mucosa. Without that, no cytoprotective effects of B12 in the digestive tube can be expected.
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PMID:Cancer incidences in the digestive tube: is cobalamin a small intestine cytoprotector? 1078 76

Tryptase is a specific marker of mast-cell activation and plays a part in the pathophysiology of various allergic diseases including asthma, but little is known of the spillover of this enzyme into the systemic circulation. Therefore, we measured serum levels of mast-cell-derived tryptase in 21 patients with mild to moderate asthma and 20 healthy, subjects, using a B12 monoclonal antibody-based immunofluoroassay that detects both monomers and tetramers of alpha- and beta-tryptases. There was a good correlation between serum and sputum tryptase levels, and, compared with healthy subjects (1.68 +/- 0.31 ng/ml), asthma patients had higher concentrations of serum tryptase (atopic asthma, 4.18 +/- 0.95 ng/ml, p = 0.022; nonatopic asthma, 3.93 +/- 0.82 ng/ml, p = 0.031). Although serum tryptase levels did not correlate with asthma symptom scores, peak expiratory flow, or forced expiratory volume in 1 s, they positively correlated with mast-cell and eosinophil counts (p = 0.041 and p = 0.025, respectively) and eosinophil cationic protein contents (p = 0.029) in induced sputum. These results suggest that serum tryptase detected with B12 antibody is a marker of allergic airway inflammation in asthma.
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PMID:Serum B12 tryptase level as a marker of allergic airway inflammation in asthma. 1209 81


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