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Biomedical subjects

E Freed

Publications and source records attributed to E Freed.

18 recordsLinked to original sources
PubMed1992

A 41-kilodalton protein is a potential substrate for the p210bcr-abl protein-tyrosine kinase in chronic myelogenous leukemia cells.

Chronic myelogenous leukemia (CML) is characterized by a translocation involving the c-abl protein-tyrosine kinase gene. A chimeric mRNA is formed containing sequences from a chromosome 22 gene (bcr) at its 5' end and all but the variable exon 1 of c-abl sequence. The product of this mRNA, p210bcr-abl, has constitutively high protein-tyrosine kinase activity. We examined K562 cells and other lines established from CML patients for the presence of phosphotyrosine (P-Tyr)-containing proteins which might be p210bcr-abl substrates. Two-dimensional gel separation of 32P-labeled proteins followed by phosphoamino acid analysis of 25 phosphoproteins, which comprised the major alkali-stable phosphoproteins, indicated that three related proteins of 41 kDa are the most prominent P-Tyr-containing proteins detected by this method. The 41-kDa phosphoproteins are found in two other CML lines that we examined but not in lines of similar lineage isolated from patients with distinct leukemic disease. A protein that comigrates with the major form of pp41 (pp41A) and contains P-Tyr is also found in murine fibroblasts and B-lymphoid cells transformed by Abelson murine leukemia virus, which encodes the v-abl protein, and in platelet-derived growth factor-treated fibroblasts, in which it has been described previously. We analyzed three pairs of Epstein-Barr virus-immortalized B-cell lines from individual CML patients and found that only the lines in which active p210bcr-abl was present contained detectable pp41. We also performed immunoblotting with anti-P-Tyr antibodies on the same CML cell lines and detected at least four other putative substrates of p210bcr-abl, which were undetected with use of the two-dimensional gel technique.

Animals↗
PubMed1989

A novel integrin beta subunit is associated with the vitronectin receptor alpha subunit (alpha v) in a human osteosarcoma cell line and is a substrate for protein kinase C.

We demonstrate that a novel integrin beta subunit is present in association with the vitronectin receptor (VNR) alpha subunit on the surface of MG-63 human osteosarcoma cells. This beta subunit and the glycoprotein IIIa beta subunit (beta 3) were both found complexed with VNR alpha on MG-63 cells and in at least two other human cell types we examined. Tryptic peptide mapping indicated that the two beta subunits are related but distinct. The novel beta chain, referred to here as beta s, was not recognized by the monoclonal antibody AP3, which recognizes GPIIIa, nor by an antiserum raised against a peptide from the COOH-terminal cytoplasmic domain of beta 3. Both receptor complexes bound to and were specifically eluted from a column containing the cell adhesion peptide GRGDSP. The unique beta subunit became phosphorylated at high stoichiometry when MG-63 cells or AG1523 human fibroblasts were treated with the phorbol-ester tumor promoter phorbol 12-myristate 13-acetate. This phosphorylation occurred mainly on serine and probably at one major site, as determined by phosphotryptic peptide mapping. Protein kinase C phosphorylated the beta s subunit of intact receptor in vitro, at the same site phosphorylated in treated cells, indicating that protein kinase C is likely to be responsible for this phosphorylation in vivo.

Electrophoresis, Polyacrylamide Gel↗
PubMed1988

HIV infection associated with symptoms indistinguishable from functional psychosis.

Patients with acquired immunodeficiency syndrome (AIDS), who present with or develop psychotic symptoms, almost invariably have evidence of cognitive impairment. Three psychotic patients, one with AIDS, and two with AIDS-related complex (ARC), who showed no evidence of cognitive impairment, are reported. It is suggested that the human immunodeficiency virus (HIV) may produce symptoms indistinguishable from those seen in the functional psychoses.

AIDS-Related Complex↗
PubMed1987

Central receptor binding and cardiovascular effects of GABA analogues in the cat.

Several structural analogues of GABA were shown to be inhibitors of GABAA receptor binding in membranes from cat cerebral cortex. These compounds were 3-aminopropanesulfonic acid (APS; IC50 = 0.04 microM), imidazoleacetic acid (IMA; IC50 = 0.4 microM), morpholinopropanesulfonic acid (MOPS; IC50 = 1.6 microM), 5-phenylpyrrolepropionic acid (PPP; IC50 = 15 microM), aminoethanethiosulfonic acid (AETS; IC50 = 22 microM), 3-amino-3-phenylpropionic acid (APP; IC50 = 35 microM), meta-aminobenzoic acid (MABA; IC50 = 58 microM) and urocanic acid (UCA; IC50 = 354 microM). The IC50 value for GABA was 0.03 microM. GABA, PPP, AETS, MABA and UCA were previously shown to reduce arterial pressure in the cat after intracerebroventricular infusion. In the present study MOPS (ED50 = 0.26 nmol/kg), APS (ED50 = 4.7 nmol/kg), APP (ED50 = 49 nmol/kg), and IMA (ED50 = 350 nmol/kg) were also found to be able to decrease blood pressure when infused into the fourth ventricle. All nine compounds reduced blood pressure to the same extent, but in some cases their relative potencies (ED50 values) exhibited significant differences. When the IC50 values for receptor binding were plotted against the ED50 values for the cardiovascular effects, no significant correlation emerged. This lack of a correlation does not necessarily imply that the reductions in blood pressure elicited by the drugs are not related to an activation of central GABAA receptors. Instead, it highlights the difficulties that are sometimes encountered in attempting to obtain quantitative measurements after intracerebroventricular infusion.

Animals↗
PubMed1986

Novel GABA analogues as hypotensive agents.

The actions of four analogues of gamma-aminobutyric acid (GABA) on blood pressure and heart rate were measured in the cat after intracerebroventricular administration. These compounds were previously found to inhibit binding to GABAA receptors of neuronal membranes from the CNS of the rat. Each of the drugs, together with GABA, produced an average maximum reduction in blood pressure of 27.63% +/- 12.5. However, aminoethanethiosulfonic acid (AETS) was the most potent (ED50 = 2.24 X 10(-10) mol/kg) of the drugs, followed by 5-phenyl-2-pyrrole propionic acid (PPP), urocanic acid (UCA), m-aminobenzoic acid (MABA) and GABA. None of the compounds produced a significant effect on heart rate. The fact that these analogues mimicked the action of GABA on the cardiovascular system of the cat and that they were able to inhibit binding to GABAA receptors, indicates that they may be GABA agonists.

Aminobenzoates↗
PubMed1983

AIDophobia.

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Acquired Immunodeficiency Syndrome↗
PubMed1982

Tardive dyskinesia.

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Depressive Disorder↗
PubMed1975

Wegener's granulomatosis: angiographic study and case report with prolonged survival.

In the limited form of Wegener's granulomatosis pulmonary arteries were pruned and slightly stretched by a cavitating granuloma. Bronchial and renal vasculature were normal. The microscopic focal small vessel changes are not appreciable at angiography. Therefore, angiography is of no value in establishing the diagnosis of Wegener's granulomatosis.

Angiography↗