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:3.2.1.17 (lysozyme)
21,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of recombinant human granulocyte colony-stimulating factor (G-CSF) on hematologic parameters was evaluated in a phase I clinical study in 18 patients with advanced malignancy. G-CSF was administered once daily as a 30-minute infusion for 14 days; three patients each were treated at increasing dose levels of 1, 3, 10, 30, and 60 micrograms kg-1 day-1. A transient decrease in neutrophil and monocyte counts was observed immediately after the G-CSF infusion, followed by a dose-dependent increase of up to 15-fold. G-CSF-induced neutrophils exhibited an increased O2- radical production, and serum levels of enzymes related to granulocyte turnover, including lysozyme and elastase, were markedly elevated during therapy. A dose-dependent depression of platelet counts occurred in the second third of the treatment course, followed by a spontaneous recovery despite continuing therapy. G-CSF was well-tolerated; minor to moderate bone pain was the most common side effect. The primary course of the malignant diseases studied was not significantly altered. G-CSF appears to be an appropriate means to selectively increase the number of functionally competent polymorphonuclear phagocytes.
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PMID:Hematologic effects of recombinant human granulocyte colony-stimulating factor in patients with malignancy. 247 25

The interaction of granulocyte-colony stimulating factor (G-CSF) and retinoic acid (RA) in proliferation and differentiation of acute promyelocytic leukemia (APL) cells was examined. G-CSF stimulated proliferation of APL cells at concentrations of 0.1 to 50 ng/ml in a dose dependent manner. More than 10(-8) M RA induced granulocytic differentiation of APL cells. Although G-CSF induced lysozyme activities in APL cells, it alone did not induce terminal differentiation of APL cells. G-CSF significantly enhanced the RA-induced granulocytic differentiation of APL cells in vitro. Enhancement by G-CSF was not due to the prolongation of survival of RA-induced differentiated cells, but the differentiation-inducing effects of G-CSF might be evident only in the presence of RA. Since G-CSF has a potential to induce the granulocytic differentiation of myeloid leukemia cells, G-CSF in combination with RA may be applicable in differentiation induction therapy for some types of myeloid leukemia.
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PMID:Granulocyte-colony stimulating factor and retinoic acid cooperatively induce granulocyte differentiation of acute promyelocytic leukemia cells in vitro. 248 63

Expression of the proto-oncogene p93c-fes and its associated tyrosine kinase activity is marked in mature granulocytes, monocytes, differentiated HL-60 leukemia cells, and leukemia cell lines KG-1, THP-1, HEL, and U-937, which can be induced to differentiate along the granulocyte/monocyte pathway. Conversely, p93-c-fes expression is absent in the K562 cell line, which is resistant to myeloid differentiation. Upon transfection and clonal selection of K562 cells using a mammalian expression vector containing the 13-kilobase pair c-fes gene, c-fes mRNA was transcribed and p93-c-fes tyrosine activity kinase was expressed. Clones expressing c-fes underwent myeloid differentiation as assessed by the appearance of phagocytic activity, Fc receptors, nitro blue tetrazolium reduction, Mac-1 immunofluorescence, and lysozyme production. These results indicate that the expression of the c-fes protooncogene and its associated tyrosine kinase activity plays a major role in the initiation of myeloid differentiation.
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PMID:K562 leukemia cells transfected with the human c-fes gene acquire the ability to undergo myeloid differentiation. 265 6

Patients receiving multiple whole blood transfusions often experience adverse clinical symptoms caused by leukocytes. In the present study, the efficacy and safety of a polyester filter for leukocytes (Sepacell R-500) was evaluated. Donor units of whole blood and red cell concentrate stored for varying lengths of time were filtered. Emphasis was placed on humoral parameters indicative of release and/or activation reactions of granulocytes (neutral proteinase elastase, lysozyme, aggregation, chemiluminescence) and erythrocytes (lactate dehydrogenase, plasma haemoglobin). Nonspecific adsorption effects were investigated by plasma protein determinations (albumin, alpha 2-macroglobulin). A complete blood cell count as well as values of haemoglobin and haematocrit were determined. Sepacell R-500 proved to be a highly efficient filter to the leukocyte depletion of blood. Our results of erythrocyte and granulocyte related humoral parameters provided no significant evidence of filtration mediated activation or releasing reactions of clinical consequence.
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PMID:Efficacy and safety of a polyester leukocyte removal filter for whole blood and red cell concentrate filtration. 276 May 69

Nedocromil sodium and cromolyn (sodium cromoglycate) are prophylactic agents in asthma which were initially found to be inhibitors of mast cell activation. Recent evidence has suggested that their effects on granulocyte-mediated reactions may contribute to their therapeutic effects. Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor (TNF) enhance the activity of granulocytes in antibody-dependent cell-mediated cytotoxicity (ADCC). Preincubation of purified neutrophils or eosinophils with nedocromil sodium or cromolyn partially inhibited their ability to mediate ADCC when stimulated by GM-CSF or TNF. Preincubation with nedocromil sodium did not alter the ability of neutrophils to produce superoxide or release lysozyme in response to soluble or phagocytic stimuli, and GM-CSF-enhanced superoxide production triggered by chemotactic peptide was not altered in such drug-treated neutrophils. After nedocromil sodium treatment, neutrophils showed no consistent changes in TNF-stimulated adherence to either plastic culture wells or umbilical vein endothelium. These findings demonstrate that nedocromil sodium and cromolyn directly and selectively affect the function of granulocytes in vitro. While drug-treated granulocytes were impaired in immune-directed cytotoxicity stimulated by GM-CSF or TNF, activation of other granulocyte functions by the same stimuli was intact.
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PMID:Nedocromil sodium and cromolyn (sodium cromoglycate) selectively inhibit antibody-dependent granulocyte-mediated cytotoxicity. 284 86

Two mouse monoclonal antibodies, L12.2 and S5.22, were developed that are specific for human neutrophilic granulocytes and produce a twofold to threefold stimulation of n-formyl-methionine-leucyl-phenylalanine (FMLP)-induced chemotaxis. Stimulation of chemotaxis by the antibodies is specific for FMLP and is concentration dependent. L12.2 appears to be more potent in stimulating chemotaxis and is isotypically distinct from S5.22. In addition, although L12.2 reacts only with mature peripheral blood granulocytes, S5.22 reacts with leukemic cells of both myeloid and monocytic origin and with immature granulocyte precursor cells. This suggests that L12.2 interacts with an antigen that appears late in the differentiation pathway, whereas S5.22 binds to an antigen that is present throughout the myeloid lineage. By means of the under-agarose and Boyden chamber techniques, L12.2, but not S5.22, by itself was also found to be a potent granulocyte chemoattractant. Cells in a gradient of L12.2 display polarized and oriented morphology. L12.2 alone, but not S5.22, also stimulates granulocyte phagocytosis and induces superoxide anion production. Neither L12.2 nor S5.22 affected the release of myeloperoxidase or lysozyme from granulocytes either alone or in combination with FMLP, C5a, or the tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate (TPA). These results suggest that L12.2 interacts with a single antigenic determinant on granulocytes that is involved in chemotaxis, phagocytosis, and superoxide anion release.
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PMID:Stimulation of human neutrophilic granulocyte chemotaxis by monoclonal antibodies. 298 Dec 60

Conditioned medium (CM) obtained from a human hepatoma cell line, SK-HEP-1, contains colony-stimulating factors (CSFs) active on murine and human bone marrow-derived granulocyte and macrophage colony-forming units (CFU-GM) and a factor capable of inducing granulocyte-macrophage differentiation (GM-DF) of murine myelomonocytic leukemic cells WEHI-3B(D+) and human promyelocytic leukemic cells HL-60 when assayed in semisolid agar cultures. The human active granulocyte-macrophage colony-stimulating factor (GM-CSF) for day 7 CFU-GM and the GM-DF for WEHI-3B(D+) and for HL-60 are not separable by acrylamide agarose column chromatography, eluting at an apparent molecular weight between 20,000 and 35,000 daltons, or by isoelectric focusing (isoelectric point, pH 5.4). In addition, SK-HEP-1 CM contains erythroid burst-promoting activity (BPA) and a factor that promotes the growth of human mixed colonies. SK-HEP-1 cells, which grow as an adherent monolayer, appear not to be endothelial or monocytic in origin since by immunofluorescent staining they are negative for Ia (HLA-DR), monocyte antigen 1 and 2, lysozyme, and factor VIII-related antigen. Positive immunofluorescent staining for keratin and fibronectin suggests the possibility that SK-HEP-1 is an epithelial cell line. Constitutive production of GM-DF as well as other hematopoietic activities including GM-CSF, erythroid BPA, and an activity that promotes the growth of human mixed colony progenitors by a human epithelial tumor cell line, SK-HEP-1, suggests that this cell line is a valuable resource for both large-scale production of these factors and the cloning of the gene(s) that code for these regulators.
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PMID:Constitutive production of leukemia differentiation, colony-stimulating, erythroid burst-promoting, and pluripoietic factors by a human hepatoma cell line: characterization of the leukemia differentiation factor. 299 Jun 10

Ten patients were treated with repeated leukophereses performed one to three times per week for 2-5 weeks. Two of the patients was cleared completely, four exhibited regression of more than one-half of the lesions, and four showed only a slight improvement. The therapy did not markedly affect the granulocyte count in peripheral blood, and the beneficial clinical response was not related to the number of polymorphonuclear leukocytes (PMNs) removed by leukophereses. During therapy, the activities of elastase, cathepsin G, lysozyme, and myeloperoxidase in PMNs were determined by spectrophotometry. PMNs isolated using a Haemonetics 30 blood-cell separator were about 50% deficient in these activities in comparison to cells obtained directly from peripheral blood. Thus, leukopheresis induces a marked degranulation of PMNs. Repeated leukophereses were found to generate significant variations in the activities of circulating PMN granule enzymes and in the levels of acid-soluble proteins. Remission or great improvement were observed in patients who, during therapy, exhibited decreased PMN elastase and cathepsin G activities, whereas a poor clinical response was accompanied by high enzymatic activities.
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PMID:Leukopheresis for treatment of psoriasis: is therapeutical benefit related to reduced activities of neutral proteinases of polymorphonuclear leukocytes? 300 6

Two chemoattractants, the peptide N-formyl-met-leu-phe (FMLP), and the ether phospholipid, platelet activating factor (PAF), each stimulate a variety of in vitro responses in polymorphonuclear leucocytes (PMN). Because often more than one inflammatory mediator is active during inflammation, we determined the effect on PMN of sequential stimulation with these two agents. Before FMLP stimulation, human PMN were exposed to PAF, at concentrations which gave little or no response when administered alone. PAF enhanced FMLP-elicited superoxide release in a dose-dependent fashion. Likewise, release of granular lysozyme from the cells was increased in PAF treated cells. Similar treatment with other phospholipids, including the lyso derivation of PAF, failed to produced these effects. Incubation with nordihydroguaiaretic acid, an inhibitor of arachidonic acid metabolism, had little effect on the enhancement of lysozyme release by PAF. To determine if enhancing effects by PAF might occur also in vivo, we studied rabbits receiving PAF and/or FMLP intravenously. When rabbits received 0.01 micrograms PAF (a dose which does not elicit the sustained neutropenia observed with higher doses of PAF) followed by 0.05 micrograms FMLP the absolute granulocyte count (AGC) dropped at 1 min (46 +/- 11% of original value), and continued to fall (24 +/- 12% at 10 min). Controls, treated with the suspending fluid for PAF, and then 0.05 micrograms FMLP, had a similar 1 min AGC value, but at 10 min AGC returned to 65 +/- 6.1% (P less than 0.001 for comparison of 10 min values). Thus PAF pretreatment enhanced FMLP-elicited granulocytopenia in vivo. Study of in vitro human PMN aggregation revealed that, at certain relative concentrations of PAF and FMLP, aggregation was enhanced. These studies show that both in vitro and in vivo responses of FMLP-stimulated PMN may be exaggerated by pre-exposure to PAF.
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PMID:In vitro and in vivo effects of treatment by platelet-activating factor on N-formyl-met-leu-phe-mediated responses of polymorphonuclear leucocytes. 303 60

Biocompatibility is redefined as the quality of being mutually tolerant with life. In so far as this represents a quality which is as likely to be achieved as is the alchemist's dream of turning lead into gold, a compromise approach is recommended. It is suggested that all extracorporeal or body invasive procedures stimulate the inflammatory defense mechanism of the body by stimulating the monocyte to produce a family of polypeptides currently known collectively as Interleukin-1 (IL-1). So far two dissimilar gene products have been cloned and there are probably more. The IL-1 group of polypeptides possess hormonal functions which orchestrate nearly every instrument of the body's defense system. Inducers of IL-1 are present in dialysate and include bacterial pyrogen and acetate. In addition bacterial cell wall glycoprotein may be cleaved into muramyl dipeptides by the release of granulocyte lysozyme at the membrane interface. Muramyl dipeptides have been found in CAPD drain fluid and are more potent inducers of IL-1 than endotoxin. Membrane activation of the fifth component of complement with the release of C5a will also induce monocytes to produce IL-1. The consequences of repeated stimulation of the acute phase response are undesirable and may include muscle wasting, osteopenia and bone cysts (Shrinking man syndrome), fibrosis of scapulo-humeral joints and the carpal-tunnel syndrome. These latter lesions are often associated with deposition of amyloid fibrils related to beta 2 microglobulin. Efforts to reduce these complications are urgently required.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Future trends in biocompatibility aspects of hemodialysis and related therapies. 349 68


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