Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recombinant human interferon-gamma (rHuIFN-gamma) was associated with liposomes in an attempt to improve its therapeutic efficiency. It was associated with liposomes composed of phosphatidylserine (PS) and phosphatidylcholine (PC) at a ratio of 3:7, and of PS:PC and cholesterol (CHOL) at a ratio of 1:4:5 with efficiencies of 13% and 21%, respectively. The lipid composition influenced the antiviral activity of the liposome-complexed IFN-gamma tested against vesicular stomatitis virus. IFN associated with PS:PC liposomes was fully bioavailable and degraded by trypsin treatment. In contrast, PS:PC:CHOL-IFN was resistant to trypsin, and appeared latent as its full biological activity was seen only after disruption of the liposomes with detergent. Four human tumor cell lines were exposed to free and liposome-associated IFN-gamma. The growth of three solid tumor lines (colon, bladder, and lung) was inhibited by similar concentrations of free IFN and PS:PC-IFN. In contrast, less PS:PC-IFN than free IFN was needed to inhibit histiocytic lymphoma cells. Higher concentrations of PS:PC:CHOL-IFN than of free IFN were needed to inhibit growth of all four cell lines. The specificity of these effects of liposome-associated IFN-gamma were shown by their partial or complete neutralization by antibody to IFN-gamma. When liposome-IFN complexes of either type were stored at 4 degrees C, 30% of the IFN activity remained after 7 days; thereafter, decay was minimal over the next 3 weeks. These data show the formation of stable HuIFN-gamma-liposomes and indicate that the lipid components of these complexes influence their antiviral and antiproliferative activity for several different cell types.
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PMID:Antiviral and antiproliferative properties of liposome-associated human interferon-gamma. 211 53

A comparative study of large cell lymphoma (LCL) (ten B and ten T), Hodgkin's disease (15 cases), and true histiocytic lymphoma (two cases) was undertaken, using formalin-fixed paraffin-embedded tissue sections, a panel of eight antibodies, and one lectin to determine if any particular antibody or immunologic profile could reliably distinguish between these entities. The antibodies used were against Leu-M1, alpha-1-anti-chymotrypsin (alpha-ACT), alpha-anti-trypsin (alpha-AT), lysozyme, kappa, lambda, leukocyte common antigen (LCA), and S-100 protein. The lectin used was peanut agglutinin (PNA). Although Leu-M1 staining was positive in 11 of 15 cases (73%) of Hodgkin's disease, it was also positive in 4 of 10 cases (40%) of T-cell lymphoma, 2 of 10 cases (20%) of B-cell lymphoma, and 1 of 2 cases (50%) of true histiocytic lymphoma. Peanut-agglutinin staining results were similar to Leu-M1. The only staining profile that emerged was the presence of Leu-M1, PNA-, alpha-ACT, and alpha-AT staining in Reed-Sternberg (RS) cells in 11 of 15 cases of Hodgkin's disease. Leu-M1 and its staining pattern is characteristic, but not entirely specific for RS cells, and it was not positive in at least 25% of the cases of Hodgkin's disease in formalin-fixed, paraffin-embedded tissues. The limitations of this antibody and others should be recognized.
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PMID:A comparative marker study of large cell lymphoma, Hodgkin's disease, and true histiocytic lymphoma in paraffin-embedded tissue. 294 20

The human monocytic leukemia cell line THP-1 produces an immunosuppressive factor that inhibits interleukin 1 (IL-1)-dependent proliferation of mouse thymocytes as well as the mitogenic effects of concanavalin A (Con A) and phytohemagglutinin (PHA) on human peripheral blood mononuclear cells. The mechanism of action of this factor includes interference with both the production of interleukin 2 (IL-2) and its effects on target cells. Thus, the suppressor abrogates the proliferation of an IL-2-dependent cytotoxic T cell line (CTLL), but not of IL-2 independent cells like the L929 fibroblasts or the EL4 T lymphoma and U937 histiocytic lymphoma lines. It also suppresses IL-2 production by human peripheral blood enriched T cells and mouse splenocytes. The mediator has a molecular weight of 60,000-70,000 dalton, as determined by gel filtration chromatography, is heat labile, and is sensitive to trypsin, chymotrypsin, and protease.
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PMID:A macrophage-derived factor that inhibits the production and action of interleukin 2. 389 22

Fifty-five cerebrospinal fluid (CSF) specimens from 42 patients with suspected meningeal tumor involvement were reviewed. Cytology in conjunction with immunocytochemistry identified 26 CSF specimens as malignant. There were fifteen cases of lymphoma, four cases of leukemia, two cases of carcinoma, and two cases of melanoma. A monoclonal light chain expression was demonstrated in nine out of eleven B cell lymphomas. The three T-cell lymphomas all expressed pan T markers (CD 3) and two the T-helper antigen (CD 4). One patient had meningeal involvement of a true histiocytic lymphoma which was identified by its large atypical cells which were positive for alpha-1-anti-trypsin and muramidase. In four patients with a primary diagnosis of acute lymphoblastic leukemia, CSF involvement was confirmed by the demonstration of blasts with CD 10 (cALLA) or light chain restriction. Epithelial or melanocytic markers were demonstrated on the tumor cells in CSF from the remaining four patients. In 29 CSF specimens a diagnosis of reactive lymphocytosis was made using cytomorphology which mostly was characterized by macrophages mixed with small mature lymphoid cells. Immunologic evaluation showed that these mature cells were CD 10 negative T-cells and only few specimens contained polyclonal B-cells. The subsequent clinical course of these patients showed no evidence of CNS malignancy. It is concluded that cytology should be used in conjunction with immunocytochemistry to accurately evaluate CSF specimens from patients with possible malignant meningitis.
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PMID:Diagnosis of lymphoma, leukemia, and metastatic tumor involvement of the cerebrospinal fluid by cytology and immunocytochemistry. 778 40

We report the purification of a protease from tumor cells undergoing apoptosis that is involved in activating DNA fragmentation. Initial studies revealed that two inhibitors of serine proteases, N-1-tosylamide-2-phenylethylchloromethyl ketone and carbobenzoxy-Ala-Ala-borophe (DK120), suppressed tumor necrosis factor or ultraviolet (UV) light-induced DNA fragmentation in the U937 histiocytic lymphoma as well as UV light-induced DNA fragmentation in the BT-20 breast carcinoma, HL-60 myelocytic leukemia, and 3T3 fibroblasts. The protease was purified by affinity chromatography with DK120 as ligand and showed high activity on a synthetic substrate preferred by elastase-like enzymes (Ala-Ala-Pro-Val p-nitroanilide), but was inactive on the trypsin substrate, N-alpha-benzyloxycarbonyl-L-lysine thiobenzyl ester, or the chymotrypsin substrate, Ala-Ala-Pro-Phe p-nitroanilide. The activity of the DK120-binding protease purified from U937 cells undergoing apoptosis was increased approximately 10-fold over that recovered from normal cells. Further purification to homogeneity by heparin-Sepharose affinity chromatography followed by reverse phase high-performance liquid chromatography revealed a single band of 24 kD on a silver-stained sodium dodecyl sulfate gel. In addition to protease activity, the purified enzyme induced DNA fragmentation into multiples of 180 basepairs in isolated U937 nuclei. These findings suggest the 24-kD protease is a novel enzyme that activates DNA fragmentation in U937 cells undergoing apoptosis.
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PMID:Purification of a 24-kD protease from apoptotic tumor cells that activates DNA fragmentation. 796 87

Tumor necrosis factor (TNF) has been shown to mediate numerous cellular responses through its interaction with two distinct types of receptor. However, the relationship between TNF receptor and the biological response is not well understood. Modulation of the number of cell surface receptors by various agents has shown a lack of direct correlation with biological responses to the cytokine. In this report, we used several approaches to investigate the relationship between TNF receptor number and an early response in human histiocytic lymphoma U-937 cells. When we examined the activation of the nuclear transcription factor kappa B (NF-kappa B), an event mediated by TNF within 10-15 min, we discovered a correlation between TNF receptor occupancy up to a certain threshold and the extent of activation of the transcription factor. In addition, by kinetically down-regulating TNF receptor expression with phorbol esters, cycloheximide, or trypsin, we determined that receptors were necessary for transduction of the TNF signal. However, 10-25% of total receptors were sufficient for optimum induction of the NF-kappa B signal. When examined in different cell lines, the activation of an early biological response was found to be related not only to the TNF receptor number but also to the type of TNF receptor. These results, overall, suggest that although TNF receptors are essential for induction of NF-kappa B, a small percentage is sufficient to fully transduce this signal.
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PMID:Role of tumor necrosis factor receptors in the activation of nuclear factor kappa B in human histiocytic lymphoma U-937 cells. 798 9