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Biomedical subjects

Y Matzner

Publications and source records attributed to Y Matzner.

At least 19 recordsLinked to original sources
PubMed1992

Subcellular localization of heparanase in human neutrophils.

The subcellular localization of a heparan sulfate degrading endoglycosidase, heparanase, was studied in human neutrophils. Unstimulated cells were disrupted by nitrogen cavitation and fractionated on a Percoll density gradient into three components, separating the plasma membranes, specific granules, and azurophilic granules. Heparanase activity was measured by gel filtration analysis of 35S-labeled degradation fragments released from subendothelial extracellular matrix (ECM) or produced during incubation with soluble, ECM-derived, heparan sulfate proteoglycans. Heparanase activity was found mainly in fractions containing the specific granules; this activity was inhibited by heparin. Freezing and thawing was not needed for recovery of the enzyme from the subcellular fraction, confirming previous data about its ready release. The mechanism of the ready release of heparanase from the specific granules requires further investigation.

Extracellular Matrix↗
PubMed1992

A potent inhibitor of platelet activating factor from the saliva of the leech Hirudo medicinalis.

Leech saliva is shown to contain protein platelet aggregation inhibitors and a range of selective low molecular weight (LMW) aggregation inhibitors. Gel filtration on Bio-Gel P-2 (cut-off kDa) yields a protein fraction (Fr. I) and three LMW fractions. Fr. I inhibits aggregation induced by collagen, ADP, epinephrine and arachidonic acid. Of all the fractions, only one, Fr. II (LMW) specifically inhibits aggregation induced by platelet activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine). Fr. II also inhibits thrombin-induced platelet aggregation. Fr. III inhibits aggregation induced by ADP, epinephrine and arachidonic acid, and Fr. IV only that induced by arachidonic acid. Fr. II also inhibits PAF- and thrombin-induced thromboxane generation in platelets, but does not inhibit arachidonic acid-induced thromboxane generation. Efforts to separate the anti-PAF from the anti-thrombin activity have been unsuccessful. The inhibition may therefore be due to a single inhibitor, though it may also be due to several inhibitors. Fr. II also inhibits superoxide anion production in formyl Met-Leu-Phe (fMLP)- and ionophore 23187- stimulated neutrophils. This may be due to the inhibition of the effects of PAF generated within the cell. Preliminary results suggest that the Fr. II inhibitor(s) is (are) amphipathic. The interaction of platelets with PAF and their interaction with the inhibitor(s) are mutually exclusive, and the inhibition may be competitive.

Animals↗
PubMed1992

Glycosylated serum ferritin in patients with hematological malignancies before and after bone marrow transplantation.

Glycosylated and total serum ferritin levels were monitored in patients with acute leukemia and lymphoma undergoing bone marrow transplantation (BMT). Serum ferritin was high in relapsing patients and normal in most patients in complete remission (CR). In patients with an uncomplicated course, levels of ferritin increased during the first month after BMT with subsequent decrease. Three patients with lymphoma and five with acute leukemia had high serum ferritin levels despite achieving apparent complete hematological remission which was of short duration. The results were compared with groups of lymphoma patients at presentation and during remission and with healthy normal controls. In all the lymphoma patients and in 3 of the 5 leukemia patients the percent of ferritin glycosylation was normal at CR. It was low at the time of diagnosis in all patients. Thus, the percent glycosylation proved a more reliable marker for clinical remission than total serum ferritin. During follow up after BMT in uncomplicated cases, the percent of glycosylated ferritin returned to normal levels earlier than the total serum ferritin. These findings indicate that the evaluation of the amount of glycosylated ferritin may provide useful information in hematological patients in whom there is a discrepancy between high serum ferritin levels and the clinical condition.

Bone Marrow Transplantation↗
PubMed1992

Expression of heparanase by platelets and circulating cells of the immune system: possible involvement in diapedesis and extravasation.

Interaction of T and B lymphocytes, platelets, granulocytes, macrophages and mast cells with the subendothelial extracellular matrix (ECM) is associated with degradation of heparan sulfate (HS) by a specific endoglycosidase (heparanase) activity. The enzyme is released from intracellular compartments (i.e., lysosomes, specific granules) in response to various activation signals (i.e., thrombin, calcium ionophore, immune complexes, antigens, mitogens), suggesting its regulated involvement in inflammation and cellular immunity. In contrast, various tumor cells appear to express and secrete heparanase in a constitutive manner, in correlation with their metastatic potential. Heparanase enzymes produced by different cell types may exhibit different molecular properties and substrate cleavage specificities. The platelet enzyme appears also in a latent form. It can be activated by tumor cells and thereby facilitate their extravasation in the process of metastasis. Degradation of ECM-HS by all cell types was facilitated by a proteolytic activity residing in the ECM and/or expressed by the invading cells. This proteolytic activity produced a more accessible substrate for the heparanase enzymes. Heparanase-inhibiting, nonanticoagulant species of heparin markedly reduced the incidence of lung metastasis in experimental animals. These species of heparin also significantly impaired the traffic of T lymphocytes and suppressed cellular immune reactivity and experimental autoimmune diseases. Heparanase activity expressed by intact cells (i.e., platelets, mast cells, neutrophils, lymphoma cells) was found to release active HS-bound basic fibroblast growth factor from ECM and basement membranes. Heparanase may thus elicit an indirect neovascular response in processes such as wound repair, inflammation and tumor development. The significant anticancerous effect of heparanase-inhibiting molecules may therefore be attributed to their potential inhibition of both tumor invasion and angiogenesis. Both normal leukocytic cells and metastatic tumor cells can enter the bloodstream, travel to distant sites and extravasate to the parenchyma at these sites. We suggest that heparanase is utilized for this purpose by both types of cells. Other functions (i.e., enzyme activities, adhesive interactions, chemotactic and proliferative responses) of metastatic tumor cells seem to mimic the equivalent functions of leukocytes as they migrate across blood vessels to gain access to sites of inflammation.

Animals↗
PubMed1990

Partial resistance to anticoagulation after streptokinase treatment for acute myocardial infarction.

This study examines the response of 3 different groups of patients to anticoagulants: 50 patients previously treated with streptokinase for acute myocardial infarction (AMI) (group 1), 24 patients with AMI who had received anticoagulants without prior thrombolysis (group 2) and 11 subjects who received anticoagulants for noncoronary indications (group 3). No significant differences were detected between groups 2 and 3; therefore, they were combined for analysis. After streptokinase, patients required 37,755 +/- 1,516 (mean +/- standard error of the mean) U of heparin per day to achieve the desired activated partial thromboplastin time (APTT). The dosage was 30,294 +/- 1,089 U/day in patients without antecedent thrombolysis (p less than 0.001). Group 1 patients required 5 +/- 0.4 days until adequate anticoagulation was achieved, compared with 3 +/- 0.2 days in the control group (p = 0.01). Despite higher heparin requirements, group 1 patients had a lower APTT value than the other subjects (87 +/- 5 vs 101 +/- 6 seconds, p = 0.08). Group 1 patients required 5 +/- 0.3 days to reach anticoagulation with warfarin versus 4 +/- 0.2 days in groups 2 + 3 (p = 0.05). Comparison of groups 1 and 2 yielded similar, although smaller, differences. Patients treated with streptokinase for AMI seem to be partially resistant to anticoagulation, which may increase the risk of reocclusion.

Anticoagulants↗
PubMed1990

Specific binding of placental acidic isoferritin to cells of the T-cell line HD-MAR.

Acidic placental isoferritin inhibited the blastogenic response of peripheral human lymphocytes to T-cell activating lectins. We measured specific binding of radioiodinated placental isoferritin to cells of the T-cell line HD-MAR and found specific high-affinity binding. Binding was faster and more ferritin was bound at 37 degrees C than at 4 degrees C. Displacement experiments indicated that most of the binding occurred at the cell surface. Acidic placental ferritin and isolated H-type ferritin subunits but not isolated L-type subunits, competed for the binding. Scatchard plot analysis showed characteristics of a single binding species with a dissociation constant (Kd) of 1.3-4.4 x 10(-11) M. The results suggest the presence of receptors for acidic isoferritin on T-lymphocytes and thus, a regulatory role for the acidic ferritin H-type subunit in T-cell function.

Binding, Competitive↗
PubMed1990

Partial characterization of a C5a-inhibitor in peritoneal fluid.

We have recently described a 40-kDa protein in peritoneal fluid that neutralized the chemotactic activity of the C fraction C5a. It was deficient in peritoneal fluids of patients suffering from familial Mediterranean fever. Further characterization of the inhibitor with the use of 125I-rC5a binding to dibutyryl cAMP-induced U937 cells revealed dependence on the peritoneal fluid concentration, on the time of incubation and on temperature and pH. Fractionation of 125I-C5a on Sephadex G-50 column, before and after incubation with peritoneal fluid, revealed similar fractionation patterns despite loss of biologic activity of the treated C5a (but not its binding to polyclonal anti-C5a antibody). Analysis of rC5a by SDS-PAGE before and after treatment with partially purified C5a inhibitor, revealed slight modification of the inhibitor-treated C5a. Using various protease inhibitors (i.e., PMSF) suggested that the C5a inhibitor is a serine protease. It neutralized C5a by means of limited proteolysis which did not change C5a immunologic properties and changed only slightly its m.w. but abolished its receptor binding and chemotactic functions. It is suggested that the C5a inhibitor plays a role in the regulation of inflammation in serosal tissues and that its deficiency in familial Mediterranean fever may explain the attacks of sterile inflammation characteristic of this disease.

Ascitic Fluid↗
PubMed1990

Selective inhibition of neutrophil activation by the subendothelial extracellular matrix: possible role in protection of the vessel wall during diapedesis.

Mobilization of circulating neutrophils toward an inflamed area involves adherence of the cells to the vascular endothelium and subsequent penetration through the endothelial cell layer without causing significant damage. To investigate the nature of a possible protective mechanism, granulocytes were incubated with the extracellular matrix (ECM) produced by cultured endothelial cells and tested for release of enzymes, chemoattractants, and free oxygen radicals. In the absence of exogenously added stimuli, the neutrophils adhered to the ECM but there was no detectable release of lysozyme, chemotactic activity, or production of O2-. In contrast, the cells readily released a heparan sulfate-degrading endoglycosidase (heparanase) to an extent comparable with that released in contact with polystyrene surfaces. Neutrophils treated with the calcium ionophore A23187 or with the peptide FMLP produced O2- to a much lesser degree when incubated in contact with ECM-coated surfaces than did those incubated in contact with uncoated polystyrene culture dishes. The ECM itself was devoid of superoxide dismutase activity. Stimulation with opsonized zymosan was not inhibited by the ECM. Experiments with isolated constituents of the ECM revealed that fibronectin but not collagen type IV or laminin could partially inhibit O2- production by Ca2+ ionophore-stimulated neutrophils. Treatment of the ECM with proteolytic enzymes, but not with heparanase, abolished its inhibitory effect on neutrophil activation. These results indicate that the subendothelial basement membrane has the capacity to inhibit release of potentially noxious agents excluding heparanase, suggesting a preferential involvement of this enzyme in neutrophil diapedesis.

Cell Adhesion↗
PubMed1990

Proposed mechanism of the inflammatory attacks in familial Mediterranean fever.

Peritoneal and synovial fluids of patients with familial Mediterranean fever lack a protein that inhibits neutrophil chemotaxis by antagonizing the complement-derived inflammatory mediator C5a. The C5a inhibitor activity was studied with the use of a C5a binding assay where peritoneal fluids were tested for their ability to inhibit recombinant C5a binding to dibutyryl cyclic adenosine monophosphate-induced U937 cells. In contrast to normal peritoneal fluids, those from patients with familial Mediterranean fever contained less than 1% C5a inhibitor activity. Gel filtration and ion exchange chromatography of peritoneal fluids from those patients did not yield any fraction that inhibited C5a binding. We suggest that the serosal tissue of patients with familial Mediterranean fever is devoid of C5a inhibitor activity and that this deficiency may explain in part the local inflammatory episodes characteristic of this disease.

Ascitic Fluid↗
PubMed1990

Effect of zinc therapy on neutrophil chemotaxis in psoriasis.

Neutrophil chemotaxis in patients with psoriasis vulgaris and psoriatic arthritis was investigated before and after 6 weeks of treatment with zinc sulphate (50 mg elementary zinc three times daily). In patients with active psoriasis vulgaris, a significant increase in neutrophil random migration and directed chemotaxis was demonstrated (10.2 +/- 3.1 and 14.1 +/- 4.1 mu, respectively, greater than that of control patients), while in patients with psoriatic arthritis the values were within the normal range (5.8 +/- 3.2 and 1.1 +/- 4.1 mu, respectively, greater than that of control patients). Although the zinc sulphate treatment had little or no effect on the course of either disease, it restored both the random migration and directed chemotaxis to normal values in psoriasis vulgaris patients. These results support the contention that zinc sulphate modifies neutrophil inflammatory potential; however, the lack of a clinical benefit suggests that neutrophils play only a secondary role in the pathogenesis of psoriasis.

Adult↗
PubMed1989

Perturbation of endothelial functions by ionizing irradiation: effects on prostaglandins, chemoattractants and mitogens.

Numerous studies have shown that early radiation injury is characterized by vascular damage and that the initial site of damage appears to be the EC lining of the vessel wall. Chronic irreversible tissue reactions to radiation include thrombotic occlusion of capillaries, enhanced atherosclerosis in larger vessels, inflammatory changes, and late tissue fibrosis. These processes may be mediated by endothelial products released as a result of cellular injury. Using EC cultures, we show that ionizing irradiation affects one of the major vascular defense mechanisms against platelet activation, thrombosis, and atherosclerosis--the capacity to produce PGI2. Dose- and time-related damage to enzymes of the arachidonic acid cascade were demonstrated. Radiation damage is associated with oxidant stress and production of free radicals. The oxygen radical scavenger, vitamin C, was found to protect the capacity of irradiated ECs to produce PGI2. Radiation injury often induces an acute inflammatory response. We found that irradiated ECs release a chemotactic factor for neutrophils, which is a lipid product of the lipoxygenase pathway. Late radiation-induced tissue fibrosis and the capacity of radiation to enhance arteriosclerosis may involve participation of mitogens released from perturbed and damaged ECs. We show that conditioned medium of irradiated ECs contain larger amounts of newly synthesized mitogens capable of stimulating the proliferation of fibroblasts, SMCs, and ECs. Hence, it may be assumed that the mitogenic activity released by irradiated ECs includes both PDGF and FGF-like mitogens.

Animals↗