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Biomedical subjects

E J Goetzl

Publications and source records attributed to E J Goetzl.

306 records · Page 17Linked to original sources
PubMed1973

The fibrinolytic pathway of human plasma. II. The generation of chemotactic activity by activation of plasminogen proactivator.

The conversion of plasminogen proactivator to plasminogen activator by Hageman factor fragments results in the generation of chemotactic activity for human neutrophils. This chemotactic activity can be distinguished from that generated by Hageman factor activation of prekallikrein and is demonstrable in plasma that is genetically deficient in prekallikrein (Fletcher factor deficiency). Both the plasminogen-activating activity and chemotactic activity produced by the interaction of Hageman factor fragments and plasminogen proactivator to yield plasminogen activator were inhibited by diisopropyl fluorophosphate (DFP) indicating an essential role for the enzymatic site in both these activities. The finding that the plasminogen proactivator tolerated a dose of DFP, which completely inactivated the plasminogen activator, reveals that the active site is protected in the precursor protein.

Blood↗
PubMed1972

A neutrophil-immobilizing factor derived from human leukocytes. I. Generation and partial characterization.

A factor has been derived from human leukocytes which irreversibly inhibits the response of human neutrophils to diverse chemotactic stimuli without impairing their viability. It is released by both polymorphonuclear and mononuclear leukocytes during incubation in acidic medium, after endotoxin exposure and subsequent incubation in low potassium medium, and during phagocytosis of particles. It is extractable from both leukocyte types and therefore must be preformed. This chemotactic inhibitor is completely separable from contaminating chemotactic activity in the crude supernatants, has a mol wt of 5000, and is inactivated by digestion with trypsin or chymotrypsin. It has been termed a neutrophil-immobilizing factor because it inhibits neutrophils directly and independently of the chemotactic stimulus, and has relatively little effect on human monocyte chemotaxis.

Blood Platelets↗
PubMed1971

A physiological approach to the assessment of disease activity in rheumatoid arthritis.

A method is described for assessing the in vivo oxygen consumption and lactate production rates of human knee joints. It is based on the rate of fall of P(o2) and the rate of rise in lactate concentration in an intra-articular saline pool after interruption of the circulation to the joint with an arterial tourniquet. Studies in 5 control patients with degenerative joint disease and 29 patients with rheumatoid arthritis showed a 2- to 3-fold higher mean oxygen uptake rate and a 10- to 12-fold higher mean lactate appearance rate in the saline in the rheumatoid joints with severe disease compared to the control joints. These metabolic variables correlated with tissue metabolic demand as estimated in synovial biopsies. (133)Xe washout from the intra-articular space, which reflects joint circulatory flow, showed a 3-fold greater mean washout rate from the rheumatoid joints (48 studies) than control joints (7 studies) with extensive overlap between the two groups. (133)Xe washout rate correlated with knee joint inflammation estimated both clinically and histologically. After synovectomy in four patients, the operated knee showed a greater fall in lactate production than the opposite knee in three of these patients. Neither knee joint oxygen uptake nor (133)Xe washout rate changed significantly. Intra-articular corticosteroid injection (eight patients) resulted in decreased lactate production and a decreased (133)Xe washout rate in the injected knee and variable results in the untreated knee. Oxygen uptake again was unchanged after therapy.

Adult↗
PubMedDate not supplied

Identification of neuropeptide-degrading enzymes in the pancreas.

Neutral endopeptidase (NEP) and aminopeptidase M (APM) were identified in the pancreas by enzymatic assays and Western blotting. The NEP activity, assessed by the phosphoramidon- and DL-thiorphan-inhibitable degradation of glutaryl-Ala-Ala-Phe-4-methoxy-2-naphthylamine, was 28.8 pmol/h/micrograms of pancreatic membrane protein and 124 pmol/h/10(6) pancreatic acinar cells. The APM enzymatic activity, assessed by the actinonin- and amastatin-inhibitable degradation of Ala-4-methoxy-2-naphthylamine, was 633 pmol/h/micrograms pancreatic membrane protein and 17.4 nmol/h/10(6) pancreatic acinar cells. Proteins corresponding to NEP (95 kDa) and APM (140 kDa) were identified in membranes by Western blotting. Both NEP and APM on acinar cells may degrade neuropeptides and regulate their effects on exocrine secretion.

Amino Acid Sequence↗
PubMedDate not supplied

Lysophospholipid enhancement of human T cell sensitivity to diphtheria toxin by increased expression of heparin-binding epidermal growth factor.

The effects of lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) on T cell expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF), the diphtheria toxin (DT) receptor, were investigated in the Tsup-1 cultured line of human CD4+ 8+ 3low T lymphoblastoma cells. Tsup-1 cells bear endothelial differentiation gene (edg)-2 and -4-encoded G protein-coupled receptors (GPCRs) for LPA and Edg-3 and -5 GPCRs for S1P. Suppression by DT of Tsup-1 cell protein synthesis was enhanced by LPA and S1P, with lipid structural specificity similar to that required for their recognition by Edg receptors. LPA and S1P increased the Tsup-1 cell level of immunoreactive HB-EGF, and neutralizing antibodies to HB-EGF inhibited LPA and S1P enhancement of Tsup-1 cell susceptibility to DT. Stabilized transfection of Tsup-1 cells with a combination of plasmids encoding Edg-2 plus -4 antisense mRNA suppressed the levels of Edg-2 and -4, but not Edg-3 and -5, in Western blots and reduced in parallel the increments in HB-EGF and susceptibility to DT evoked by LPA but not S1P. Similar transfection with Edg-3 plus -5 antisense plasmids suppressed Tsup-1 cell levels of immunoreactive Edg-3 and -5, but not Edg-2 or -4, and concurrently reduced S1P-, but not LPA-, induced Tsup-1 cell increases in both HB-EGF and susceptibility to DT. Edg GPCR-mediated LPA and S1P enhancement of T cell sensitivity to DT, thus, may be attributable to increased expression of the DT receptor HB-EGF.

Cell Line↗
PubMedDate not supplied

Neuropeptide signaling of lymphocytes in immunological responses.

Peptidergic nerves in immune organs and lymphoid tissues of the lungs and gastrointestinal tract end on or in close proximity to lymphocytes, mast cells and macrophages. Vasoactive intestinal peptide, substance P and some other neuropeptides, that are recognized by distinct sets of cell surface receptors, regulate aspects of T cell differentiation in the thymus, such as negative selection, and contribute to mediating compartmental immune responses. The latter effects include stimulating expression of adhesive proteins by lymphocytes, enhancement of lymphocyte and macrophage migration in vascular and connective tissues, and modulation of proliferative and synthetic responses of lymphocytes to diverse antigens.

Animals↗