The epidermal growth factor receptor and its ligands.
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Amino Acid Sequence↗
Biomedical subjects
A Wells
Publications and source records attributed to A Wells.
Keratoconjunctivitis sicca with associated secondary uveitis elicited in rats after systemic xylazine/ketamine anesthesia.
The systemic administration of an anesthetic dosage of a combination of xylazine and ketamine hydrochloride produced an acute exposure keratopathy which progressed into a syndrome resembling keratoconjunctivitis sicca. Within a few minutes corneal changes occurred that were characterized by viscous mucus, loss of corneal luster and dryness. Other acute but transient changes included development of cataracts, mydriasis and proptosis. Progressive changes were observed in the cornea within 4 days which lasted at least 8 weeks in some cases, and included punctate epithelial keratopathy progressing to devitalized or keratinized epithelial plaques. Polymorphonuclear cell infiltration of the corneal stroma associated with plaques occurred. Epithelial denudation and neovascularization of the cornea, dilation and engorgement of iridial blood vessels, as well as flare in the anterior chamber were also seen. The ocular lesions induced by xylazine/ketamine should be considered carefully when designing or interpreting research on the anterior segment. Ketamine hydrochloride with sodium pentobarbital produced excellent anesthesia without any significant ocular side-effects and may be preferred in many instances.
Animals↗
Shear elasticity of KxRb
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Journal Article↗
Random fields and orientational order in Rb(CN)xBr1-x mixed crystals: A study of static-shear elasticity.
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Journal Article↗
Genetic determinants of neoplastic transformation by the retroviral oncogene v-erbB.
The retroviral oncogene v-erbB is a mutant version of the gene (c-erbB or ERBB1) that encodes the cell-surface epidermal growth factor receptor (EGFR). The mutations take three forms: (i) a large deletion that removes the entire ligand-binding domain of EGFR, (ii) smaller deletions that affect the carboxyl-terminal domain of EGFR, and (iii) point mutations that cause conservative substitutions of amino acids. Previous work has shown that, in the absence of the large deletion, ERBB1 cannot transform cells autonomously. Here we report that when the large deletion is present, no other mutation is required for ERBB1 to transform established rodent fibroblasts to a tumorigenic phenotype. In particular, there is no need for deletions affecting the carboxyl terminus of the gene product. It appears, therefore, that removal of the ligand-binding domain from the EGFR suffices to create a transforming protein. Deletions at the carboxyl terminus of the EGFR apparently play only a secondary role in transformation by affecting the host range and perhaps the potency of transformation; and there is as yet no evidence to implicate point mutations in the activation of ERBB1 to an oncogene. Our findings support the view that augmented activity of the EGFR can contribute to tumorigenesis.
Alleles↗
Amplified gene for the epidermal growth factor receptor in a human glioblastoma cell line encodes an enzymatically inactive protein.
The gene encoding the receptor for epidermal growth factor was amplified two- to fivefold in the human glioblastoma cell line SF268. The amplified gene gave rise to abundant quantities of receptor that bound EGF with a high affinity (Kd, 0.35 nM). The binding of ligand failed to elicit cellular DNA synthesis, however, and the receptor was enzymatically inactive. We presume that the amplified receptor gene carries a mutation(s) that affects several aspects of the receptor's function. Characterization of the mutation(s) may illuminate how structure dictates function in the receptor protein.
Cell Cycle↗
Insulin-like and insulin-inhibitory effects of monoclonal antibodies for different epitopes on the human insulin receptor.
Monoclonal antibodies previously shown to react with five distinct epitopes on the human insulin receptor were tested for their metabolic effects on isolated human adipocytes. Two antibodies which reacted with receptor alpha-subunit and completely inhibited 125I-insulin binding mimicked the actions of insulin to stimulate lipogenesis from [14C]glucose and to inhibit catecholamine-induced lipolysis. On a molar basis, these antibodies were comparable in potency with insulin itself. Two other antibodies which decreased insulin binding only slightly or not at all also mimicked these metabolic effects of insulin. One of these antibodies reacted with receptor beta-subunit. In contrast, a further antibody which reacted with alpha-subunit and inhibited insulin binding did not affect basal lipogenesis or catecholamine-induced lipolysis, but was able to antagonize the effects of insulin on these processes. The same antibody antagonized the insulin-like effect of another antibody with which it competed in binding to insulin receptor, but not the effect of an antibody which bound independently to the receptor. It is concluded that binding of ligand at or close to the insulin-binding site is neither necessary nor sufficient to trigger insulin-like metabolic effects, which may rather depend on some general property of antibodies, such as their ability to cross-link and aggregate receptor molecules.
Adipose Tissue↗
Uveitis and arthritis induced by systemic injection of streptococcal cell walls.
A single injection of an aqueous suspension of group A streptococcal peptidoglycan-polysaccharide complexes (PG-PS) when injected intraperitoneally into Lewis rats induced a self-limiting bilateral uveitis with associated perpetuating polyarthritis. The uveitis was characterized clinically during the first 72 h by iritis and fibrin deposition. Acutely, there was infiltration of polymorphonuclear cells. The symptoms gradually subsided, and at the close of the experiment eyes were normally clinically and histologically. In contrast, perpetuating inflammation and severe tissue injury developed in the limb. Using an enzyme immunoassay with specificity for the group A streptococcal polysaccharide, the levels of PG-PS in tissues of animals that were killed 1 to 7 days post-injection were measured. The relative amounts of antigen in eye:limb:liver of PG-PS injected animals were 1:9:170. The differences in the amounts of antigen detected in the eye and limb may help explain the development of the acute uveitis in contrast to the perpetuating polyarthritis observed on PG-PS administration. The authors suggest that bacterial debris may act similarly in causing ocular inflammation in man.
Animals↗
Relationship between private self-consciousness and anxiety scores in threatening situations.
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Adolescent↗
Epstein-Barr virus binding to virus-carrying cell lines is enhanced in the presence of C3 and C3d.
The relationship between the receptors for the Epstein-Barr virus (EBV) and the C3d fragment of complement was investigated at the molecular level. In the presence of cell-bound C3, virus binding was enhanced in EBV genome-carrying lines. An identical effect could be elicited by C3d at one-quarter the weight amount; C3b and methylamine-treated C3 had no effect on virus binding. The minimum concentration of C3 which produced significant enhancement was 25 micrograms/ml. Virus binding increases were observed only after 20 min of complement-cell co-incubation. The response was not noted with EBV-negative lines and was independent of virus strain assayed (B95-8 and P3HR-1). These studies suggest that the binding sites for the two moieties are distinct, although they both involve the same cell surface complex. The two receptors are believed to display cooperativity.
Cell Line↗
The Epstein-Barr virus receptor is distinct from the C3 receptor.
Polyvalent serum directed against C3 receptors was employed in an attempt to block Epstein-Barr virus (EBV) binding to virus receptor-containing cell lines. The serum eliminated 90% of virus binding to Daudi and BJAB, lines which express only the C3d receptor. Raji and Ramos cells, which express the C3d, C3b and C3bi receptors, still adsorbed 70% of their virus capacity in the presence of excess antiserum. These effects were independent of the virus strain. In the light of previous reports, these data imply that, although the two receptors, EBV and C3d, are closely associated, the binding sites of EBV and complement are distinct. Additionally, an unusual EBV substrain-specific receptor found on U698 and P3HR-1/ASNP lines was shown to be independent of complement receptors.
Animals↗
Receptors for the complement C3d component and the Epstein-Barr virus are quantitatively coexpressed on a series of B-cell lines and their derived somatic cell hybrids.
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Animals↗
Quantitative comparison of Epstein-Barr virus receptor expression on sIgM and sIgG cell lines and B-cell lymphoma biopsies.
Over 50 B-cell derived lines and B-cell lymphoma and leukemia biopsies were screened for expression of the Epstein-Barr virus (EBV) receptor. The 13 sIgM-positive lines bound more than five times as much virus as the six IgG lines. Among the biopsies, the 17 sIgM, 11 sIgM and sIgD, and seven sIgG expressing biopsies were further divided according to expression of the C3 receptor. C3 receptor-positive biopsies, which expressed sIgM alone or along with sIgD, had the largest subpopulation of cells which expressed the EBV receptor (EBVR). C3 receptor-negative biopsies only expressed the EBVR on half as many cells as their C3 receptor-positive counterparts. However, the relative number of EBVR on individual EBVR-positive cells was independent of C3 receptor expression. Within the sIgG class, both C3 receptor-negative and positive cells expressed equally low levels of EBVR, both in terms of subpopulation and relative number of EBVR per positive cell. These results suggest that subpopulation expression of the EBV receptor is related to the C3 receptor but that relative number of receptors per cell is associated with sIg phenotype.
B-Lymphocytes↗
Two large virion envelope glycoproteins mediate Epstein-Barr virus binding to receptor-positive cells.
The four major Epstein-Barr virion envelope components were separated by column chromatography and reconstituted into artificial liposomes. These liposomes were tested for their ability to bind selectively to Epstein-Barr virus receptor-positive cells. Only when the two high-molecular-weight glycoproteins, VE1 and VE2, were present together was a stable binding complex formed. The addition of the other virion envelope components did not increase the levels of binding. This binding was inhibited by unlabeled viable virions and by neutralizing antisera, which recognized the two components. Adsorption of viable virus was also eliminated by the antisera. The enzyme susceptibility pattern of the cell-liposome interaction is similar to that of the virus-cell interaction, thus confirming the specificity of the binding site. A model for Epstein-Barr virus binding in which VE1 and VE2 coordinately recognize the same binding site is presented.
Antibodies, Viral↗
Difference in viral binding between two Epstein-Barr virus substrains to a spectrum of receptor-positive target cells.
Radio-labelled Epstein-Barr virus (EBV) was utilized in a direct binding assay to detect the presence of EBV receptors. The sensitivity of this method was affirmed by the detection of EBV-receptors on three EV-carrying cell lines that have previously been reported as receptor negative. Two laboratory substrains of EBV, derived from the cell lines B95-8 and P3HR-I (designated B and P virus respectively), were tested in the binding assay. The main repcptor prototype adsorbed both viral strains without apparent distinction. In contrast, two lines, a Swedish EBV-negative B-cell lymphoma (U698) and a virus non-producer subline of the receptor-negative P3HR-1 line, adsorbed P virus selectively but failed to adsorb B virus.
Binding, Competitive↗
A microassay for quantitatively detecting the Epstein-Barr virus receptor on single cells utilizing flow cytometry.
A quantitative microassay for detecting and analyzing the Epstein-Barr virus receptor (EBVR) utilizing fluorescein-conjugated virions is presented. The test is virus substrain-specific. Both the B95-8 and P3HR-1 strains were labelled and adsorbed to a variety of targets. Relative binding of virus was assessed by flow cytometry, the results being directly comparable with those obtained by earlier methods. Cell size and cellular DNA content were measured simultaneously with virus binding, thus enabling us to calculate EBVR density and to correlate receptor synthesis and cell cycle stage.
Cell Line↗
The detection of Epstein-Barr virus receptors utilizing radiolabelled virus.
Epstein-Barr virus (EBV) was labelled with 3H-thymidine and purified about 1000-fold from the culture medium by ultracentrifugation on 5 to 30% dextran gradients. The presence of the virus was monitored by radioactivity and Epstein-Barr virus-determined nuclear antigen (EBNA) induction in sensitive indicator cells (Ramos). Peaks for both activities occurred in the 17 to 18% dextran fractions. Unlabelled virus recovered in the peak fraction was labelled with 125I. Both thymidine and 125I-labelled purified virus bound quantitatively to receptor-positive Burkitt lymphoma-derived cell lines but not to EBV-receptor-negative T-lymphocyte-derived cell lines. Thymidine-labelled virus that was allowed to bind to Raji cells was present in the interior of briefly trypsinized cells after 3 h incubation at 37 degrees C. The results provide a convenient method for detecting the EBV receptor by radioactively labelled virus.
Burkitt Lymphoma↗
Cell surface glycoprotein patterns of two EBV-negative lines and their EBV converted sublines.
Cell surface galactosyl-glycoprotein patterns were compared between Ramos and BJAB, two Epstein-Barr virus (EBV)-negative Burkitt lymphoma lines, and their acutely EBV-superinfected and stably EBV-converted derivatives. A major difference between Ramos and its EBV-infected variants was the appearance of a 69,000 mol. wt. galactosyl-glycoprotein (GP69) in the latter. The same phenomenon was found in BJAB along with the additional appearance of a 71,000 mol. wt. galactosyl-glycoprotein (GP71) in the EBV-infected cells. GP71 was present in Ramos and in its EBV-converted derivatives.
Burkitt Lymphoma↗