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)

Vibrio cholerae neuraminidase (VCN) treatment of donor bone marrow cells results in a reduction in the number of hematopoietic colonies (CFUs) formed in the spleens of lethally irradiated mice. Treatment of marrow cells with sodium periodate under mild conditions, known to preferentially oxidize sialic acid, also reduced CFUs while subsequent potassium borohydride reduction restored CFUs to 80% of control levels. Innoculum viability as measured by in vitro incorporation of tritiated precursors into proteins, nucleic acids, and oligosaccharides was unaffected by VCN treatment. The ability of bone marrow cells in culture to respond to the hormone erythropoietin, as measured by the incorporation of 59Fe into cyclohexanone-extractable heme, was also not affected by neuraminidase, making a cytotoxic effect of the VCN preparation unlikely. Incubation of VCN-treated marrow with either beta-galactosidase or trypsin had no effect on the VCN-induced reduction in CFUs. These results are consistent with the idea that membrane sialic acid plays a direct and specific role in the implantation and development of CFUs.
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PMID:Sialic acid: a specific role in hematopoietic spleen colony formation. 73 8

We recently reported the development of three monoclonal antibodies (MoAbs) to biologically active human erythropoietin (Ep). In the present study, we investigated the epitope specificity of these three antibodies, as well as their reactivity with Eps derived from species other than man. All three antibodies reacted with the Ep polypeptide itself, rather than with its carbohydrate moieties. Moreover, all three antibodies recognized separate nonoverlapping epitopes. Further studies with reduced/alkylated Ep and with sodium dodecyl sulfate-denatured Ep suggested that two of the MoAbs, anti-Ep-2 and anti-Ep-16, were specific for conformational, nonlinear determinants on the Ep molecule, whereas the third MoAb, anti-Ep-26, appeared to recognize a linear epitope. However, anti-Ep-26 did not react with synthetic peptides representing the 26 amino-, the 99-129 mid-region, or the 10 carboxy-terminal residues of Ep, nor with trypsin-, chymotrypsin-, or V8 protease-digested fragments of Ep. When tested with Ep from different species, the neutralizing capabilities of the three MoAbs were clearly different. Comparing their effectiveness against baboon, ovine and murine Ep, antibody 2 was most effective at neutralizing baboon Ep, antibody 16 was most effective against murine Ep, and antibody 26 showed little reactivity with any of these nonhuman Eps. Because these various Eps readily stimulate across species barriers, it is likely that the receptor binding domain on Ep has remained relatively conserved during evolution. Our results therefore suggest that the neutralizing capacity of our three anti-Ep MoAbs is caused not by binding directly to the Ep receptor binding domain on Ep, but by binding to distant regions, causing conformational changes in Ep, or by binding to regions close to the binding site, steric hindrance.
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PMID:Immunochemical analysis of monoclonal antibodies to human erythropoietin. 168 48

Chromosome studies were carried out after a 24-hour harvest of unstimulated bone marrow aspirate cell cultures from a 75-year-old male with a clinical diagnosis of acute myelomonocytic leukemia (FAB M4). Analysis of nine cells after trypsin-Giemsa banding (GTG) revealed two cell lines with a mosaic chromosome pattern, 46,XY/46,XY,t(7;19)(q22;p13.3). A review of the recent literature reveals one case of childhood ALL with a 46,XY/46,XY,t(7;19)(q11;q13) chromosome pattern [1] and a 46,XY,t(3q;11q),t(7q;19p),t(15;17)(q26;q22) in one patient with ANLL (FAB M3) [2]. The t(7;19)(q22;p13.3) seen in our case has not been reported as the sole specific clonal chromosome rearrangement in myeloid neoplasia. Interestingly, the plasminogen activator inhibitor type I, multi-drug resistance, and erythropoietin genes are located at band 7q22 and the insulin receptor gene is located at band 19p13.3. Both sites contain fragile site loci. The possible role of these fragile sites, genes, or other genes in the rearrangement can only be surmised.
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PMID:Atypical (7;19) translocation in acute myelomonocytic leukemia. 175 94

The proliferation of mucosal mast cells (MMC) depends on the presence of interleukin 3 (IL 3) and can be further enhanced by interleukin 4 (IL 4). The supernatant of a TH2 cell clone (ST2/K.9) stimulated by concanavalin A was found to contain a factor, provisionally termed mast cell costimulatory activity (MCA), that substantially enhances the proliferation of MMC promoted by a combination of IL 3 and IL 4. In comparison to other lymphokines MCA is rather resistant to tryptic digestion but is very sensitive to pH values lower than 6.0 and to organic solvents. Chromatographic fractionation of MCA revealed that activity is associated with protein(s) or glycoprotein(s) of 35 to 40 kDa. Partially purified MCA that was functionally free of other T-cell-derived lymphokines did not stimulate mast cell proliferation in the absence of a combination of IL 3 and IL 4. In addition, MCA did not affect the proliferation of mast cells when employed together with either IL 3 or IL 4 alone. Control experiments demonstrated that MCA is identical to neither the T-cell-derived lymphokines IL 2 to IL 6, IL 9, interferon gamma, tumor necrosis factor alpha or beta, or granulocyte-macrophage colony-stimulating factor (CSF), nor to IL 7, granulocyte CSF, macrophage CSF, erythropoietin, leukemia inhibitory factor, or epidermal growth factor (EGF). Finally, experiments using a panel of PPD-reactive TH1- and TH2-like cell lines revealed that MCA is preferentially produced by TH2 cells. These data, especially the relative resistance of MCA to trypsin and the high sensitivity to low pH values and organic solvents, indicate that MCA is distinct from known T-cell-derived lymphokines.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of a T-cell-derived mast cell costimulatory activity (MCA) that acts synergistically with interleukin 3 and interleukin 4 on the growth of murine mast cells. 210 34

Capillary hemangioblastoma is a tumor known to be associated with secondary polycythemia. Therefore, specimens from ten hemangioblastomas were studied by immunohistochemistry for the presence of erythropoietin, renin substrate, and for various endothelial, histiocytic and glial markers. In all tumors scattered cells among the stromal cells showed a positive-staining reaction with both anti-erythropoietin and anti-renin substrate. The same cells also stained positively for alpha-1-anti-trypsin. It is concluded that, in addition to the capillary endothelial cells, pericytes and stromal cells, capillary hemangioblastomas harbor cells containing and perhaps producing renin substrate and/or erythropoietin or a substance with similar antigenic determinants.
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PMID:Erythropoietin in capillary hemangioblastoma. An immunohistochemical study. 331 72

We have previously shown that human megakaryocyte colony-stimulating activity (Meg-CSA) is present in sera from patients with bone marrow megakaryocyte aplasia. In this report, we demonstrate that Meg-CSA is also present in sera from dogs rendered aplastic by 1000 rad total body irradiation. Canine serum Meg-CSA has activity comparable to human when assayed in plasma clot cultures containing human bone marrow mononuclear cells. Because of the uniform high potency and ready availability of aplastic canine sera, it was utilized initially for Meg-CSA purification. Sequential ammonium sulfate precipitation to approximately 80% saturation resulted in recovery of 59%-69% of the serum protein and of 75%-103% of the original serum Meg-CSA. The fraction precipitable between ammonium sulfate saturations of 0% and 44%-50% (fraction I) contained 53%-76% of the initial serum Meg-CSA and 25%-32% of the initial serum protein. This represents an enrichment of Meg-CSA specific activity by over 100%. The Meg-CSA eluted from Sephacryl S-300 in a single peak corresponding to a molecular weight of 175,000. This Meg-CSA peak also contained IgG, but the Meg-CSA did not bind to protein A-agarose. Meg-CSA was 90% inactivated by trypsin digestion for 4 h at 37 degrees C and by exposure to 5mM dithiothreitol for 2 h at room temperature. Exposure to either 6 M guanidine for 1 h at room temperature or 8 M urea for 1 h at 4 degrees C resulted in a 70% loss of Meg-CSA. At culture concentrations capable of stimulating maximal megakaryocyte colony formation, fraction I supported no colony growth by myeloid (CFU-GM) or late erythroid (CFU-E) human hematopoietic progenitor cells. Erythroid burst-promoting activity (BPA) was not detected in fraction I from two of three different aplastic canine sera tested. Therefore, Meg-CSA is functionally distinct from granulocyte-monocyte colony-stimulating factor (GM-CSF), erythropoietin, and BPA. The data indicate that serum Meg-CSA is a 175,000-dalton protein (megakaryocyte colony-stimulating factor, Meg-CSF) in which higher order structure and disulfide bonding are necessary for biologic activity. Partially purified Meg-CSF manifests functional specificity for the CFU-Meg hematopoietic progenitor cell.
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PMID:Human megakaryocyte colony-stimulating factor in sera from aplastic dogs: partial purification, characterization, and determination of hematopoietic cell lineage specificity. 387 46

We have measured plasma N-acetyl-beta-D-glucosaminidase (EC 3.2.1.30) and neuraminidase (EC 3.2.1.18) activities as markers of glycosidase activity and immunoreactive trypsin (EC 3.4.21.4) levels as a marker of proteolytic potential in the plasma of normal and uraemic subjects. The levels of all of these enzymes are significantly elevated in the plasma of uraemic subjects when compared to normal. We have postulated that the combined attack of glycosidases and proteases on erythropoietin will lead to fragmentation of this glycoprotein hormone with loss of activity. This may be a major contributory cause to the anaemia of chronic renal failure.
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PMID:Increased plasma glycosidase and protease activity in uraemia: possible role in the aetiology of the anaemia of chronic renal failure. 390 90

When a single cell suspension of human adult marrow or fetal liver is treated briefly with trypsin, the number of erythroid bursts arising in culture is significantly increased. Erythroid colonies show less stimulation. The time to reach maximum burst number may also be shortened. The absolute increase in burst number is greater at higher concentrations of erythropoietin, suggesting a synergistic effect of trypsin treatment with that of erythropoietin. Trypsin also increases the size of the individual burst subunit. The trypsin effect is not limited to a given class of bursts as distinguished by subunit number. Other enzymes, pronase, chymotrypsin and phospholipase D, also increase burst number but to a lesser degree. The burst-stimulating effect of trypsin is enzymatic since it is completely prevented by DFP, a specific inhibitor of trypsin action.
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PMID:Trypsin enhances erythropoiesis in vitro. 740 Jun 71

The extracts from rat submandibular glands (SMGs) induced erythroid differentiation of K-562. The activity was non-dialysable and abolished by heat, trypsin or 2-mercaptoethanol. Follistatin, which neutralizes the erythroid differentiation factor (EDF), had no effects on this activity. Analysis by gel chromatography and polyacrylamide gel electrophoresis-isoelectric focussing showed that the characteristics of this substance were different from those of erythropoietin, TGF-beta 1, EDF, stem cell factor and insulin-like growth factor-1. These results suggest the presence of a novel substance in rat SMGs which induces erythroid differentiation of K-562.
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PMID:The extracts from rat submandibular glands induce the erythroid differentiation of K-562 cells. 759 52

Mast cell neutral proteases are the most precise markers of heterogeneity among human mast cells. Two types of human mast cells have been recognized. MCTC cells contain tryptase together with chymase, cathepsin-G like protease, and mast cell carboxypeptidase; MCT cells contain tryptase, but lack the other neutral proteases present in MCTC cells. All mast cells develop from hemopoietic stem cells. In vitro procedures for studying mast cell growth have been developed, using the major human mast cell growth factor, stem cell factor (SCF, also called Kit-ligand). Cultures of hemopoietic progenitor cells in the presence of SCF alone result in selective differentiation to mast cells. The same progenitor cells can be induced to differentiate into other lineages when SCF is used with various lineage-specific colony-stimulating factors such as erythropoietin for erythrocytes. Mast cell development from hematopoietic progenitors may represent a "default pathway," occurring optimally in a permissive microenvironment such as skin, bowel, and lung. The presence or absence of certain cytokines in blood and bone marrow may create a non-permissive environment, thus the absence of granulated mast cells in such locations.
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PMID:Human mast cell heterogeneity. 772 Oct 78


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