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M M Kay

Publications and source records attributed to M M Kay.

At least 55 records · Page 3Linked to original sources
PubMed1988

Erythrocyte aging: a comparison of model systems for simulating cellular aging in vitro.

Senescent cell antigen (SCANT) is a "neo antigen" that appears on the surface of normal old cells and initiates IgG binding and cellular removal. To investigate the mechanism by which SCANT is generated from its parent molecule, band 3, we subjected intact human erythrocytes to treatments that have been reported to result in changes in band 3 and/or to mimick aging in vitro. The validity of these treatments as model systems for erythrocyte aging was evaluated using a "red cell aging panel" that provides a biochemical profile of a senescent red cell. Treatments were assessed for their ability to induce in vitro the following changes observed in normal erythrocytes aged in vivo: 1 increased breakdown of band 3 as detected by immunoblotting, 2 decrease in anion transport efficiency as detected with a sulfate self-exchange assay, 3 decrease in total glyceraldehyde 3-phosphate dehydrogenase activity with an increase in membrane-bound activity, and 4 increase in the binding of autologous IgG as detected with a protein A binding assay. Neither incubation with the free radical-generating xanthine oxidase/xanthine system, nor treatment with malondialdehyde, and end product of free radical-initiated lipid (per)oxidation, results in age-specific changes. Loading of the cells with calcium and oxidation with iodate results in increased breakdown of band 3, but does not lead to increased binding of autologous IgG. Only erythrocytes that have been stored for 3-4 weeks show the same structural and functional changes as observed during aging in vivo.

Anion Exchange Protein 1, Erythrocyte↗
PubMed1986

Oxidation as a possible mechanism of cellular aging: vitamin E deficiency causes premature aging and IgG binding to erythrocytes.

Senescent-cell antigen is a "neo-antigen" that appears on the surface of senescent cells and initiates IgG binding and cellular removal. As an approach to evaluating oxidation as a possible mechanism for generation of senescent-cell antigen, we studied erythrocytes from vitamin E-deficient rats. Vitamin E is localized primarily in cellular membranes. Its major role is the termination of free-radical chain reactions propagated by the polyunsaturated fatty acids of membrane propagated by the polyunsaturated fatty acids of membrane phospholipids. Results of our studies indicate that erythrocytes of all ages from vitamin E-deficient rats behave like old erythrocytes from normal rats, as determined by their susceptibility to phagocytosis, IgG binding, anion transport ability, and glyceraldehyde-3-phosphate dehydrogenase activity. Increased breakdown products of band 3 were observed with immunoblotting in membranes of erythrocytes from vitamin E-deficient rats. Breakdown products of band 3 are known to increase as cells age in normal individuals. The data suggest that oxidation may be a possible mechanism for erythrocyte aging and generation of senescent-cell antigen in vivo.

Anemia, Hemolytic↗
PubMed1986

Differentiation of regulatory cell interactions in aging.

Age-related changes in different regulatory processes are polymorphic and differ in different strains and organs in terms of onset and progression. Membrane changes have been observed in terms of the association between receptors and class I major-histocompatibility-complex molecules as well as in terms of structural modification of membrane molecules. Various nutritional strategies can differentially affect age of onset and rate of progression. Tumor incidence and progression increase with age; and interesting exception has been described. Principles of experimental design for the exploration of aging processes and evolutionary aspects of aging processes are being discussed. Identification of alleles, which affect initiation and progression of deleterious aging processes, are being considered for their potential in strategies for preventive medicine.

Aging↗
PubMed1985

Cardiogenic shock associated with calcium-channel and beta blockers: reversal with intravenous calcium chloride.

Two cases in which oral ingestion of beta blocker and slow calcium-channel blocker was associated with profound hypotension and bradycardia are reported, including one case in which serum levels of both drugs were documented in the normal range at a time of severe clinical toxicity. Though unresponsive to usual therapeutic interventions, both patients showed an immediate and dramatic response to intravenous calcium chloride. It is recommended that intravenous calcium chloride be considered in any patient using routine doses of these two agents who presents with hypotension and/or bradycardia.

Adrenergic beta-Antagonists↗
PubMed1985

Glucose transport protein is structurally and immunologically related to band 3 and senescent cell antigen.

Senescent cell antigen, a polypeptide that appears on the surface of senescent and damaged cells, has been shown to be derived from band 3. In the present study, the relationship between the as yet unidentified glucose transporter and senescent cell antigen is examined. Since cytochalasin B is a specific and potent competitive inhibitor of glucose transport in human erythrocytes, the glucose transport carrier was isolated by affinity chromatography on cytochalasin B-Sepharose 4B columns and eluted with D-glucose. This purification procedure is both a method of isolation and a functional assay for the glucose transporter. Purified glucose transporter gave a sharp, single band at Mr approximately equal to 60,000 when analyzed by NaDod-SO4/PAGE. Glucose transporter was identified in erythrocyte membranes by the immunoblotting technique, using both antibodies raised against purified glucose transporter and anti-idiotypic antibodies. Two-dimensional peptide mapping revealed substantial peptide homology between glucose transporter and senescent cell antigen. In addition, the glucose transporter shared peptide homology with band 3 and its defined proteolytic fragments located toward the carboxyl terminus of band 3. Peptide homology between glucose transporter and the Mr approximately equal to 41,000 cytoplasmic segment of band 3 that contains the amino terminus could not be demonstrated. Thus, glucose transporter appears to be part of or derived from band 3, and to share substantial peptide homology with senescent cell antigen.

Anion Exchange Protein 1, Erythrocyte↗
PubMed1985

Human erythrocyte membrane proteins of zone 4.5 exist as families of related proteins.

An analysis of the polypeptide composition of zone 4.5 of human erythrocyte membranes has been done by immunoautoradiographic and two-dimensional peptide mapping techniques. Results of these studies demonstrated that the Coomassie blue profile was constant, with 14 well-resolved bands present. Zone 4.5 polypeptides existed as at least four families of two or more components with closely related polypeptide backbones. The families could be distinguished on the basis of their extraction characteristics, immunological cross-reactivity, and two-dimensional peptide maps. One family was related to protein 4.1, one family was related to band 3, and two families were independent and not similar to other larger membrane proteins. The data show that all of the visualized bands in zone 4.5 do not have the same protein composition and that several closely related forms of some polypeptides are present.

Blood Proteins↗
PubMed1985

Senescent cell antigen: a terminal differentiation antigen.

Investigations into mechanisms by which macrophages distinguish mature from senescent self cells revealed that a approximately 62,000 Mr glycoprotein, the senescent cell antigen, a terminal differentiation antigen, appears on the surface of senescent and damaged cells. It is recognized by the antigen-binding Fab region of a specific IgG autoantibody in serum which attaches to cells carrying the senescent cell antigen and initiates their removal by macrophages. The senescent cell antigen was first observed on the surface of senescent human erythrocytes, but has since been demonstrated on the surface of lymphocytes, polymorphonuclear leukocytes, platelets, embryonic kidney cells and adult liver cells.

Animals↗
PubMed1985

Aging of cell membrane molecules leads to appearance of an aging antigen and removal of senescent cells.

Investigations into mechanisms by which macrophages distinguish mature from senescent self revealed that a Mr approximately 62,000 glycoprotein, the senescent cell antigen, appears on the surface of senescent and damaged cells. It is recognized by the antigen-binding Fab region of a specific IgG autoantibody in serum which attaches to cells carrying the senescent cell antigen and initiates their removal by macrophages. The senescent cell antigen was first observed on the surface of senescent human erythrocytes but has since been demonstrated on all cells examined. Senescent cell antigen appears to be derived from band 3, the major anion transport protein of the erythrocyte. The current working hypothesis is that degradation of band 3 causes a conformational change in its tertiary structure that generates the senescent cell antigen.

Anion Exchange Protein 1, Erythrocyte↗
PubMed1985

Age effects on colony-forming human peripheral blood T and B cells.

An assay was developed for studying the effect of age on human colony-forming T and B cells. Phytohemagglutinin was used to induce the formation of T cell colonies and anti-human Fab antibodies were used to induce the formation of B cell colonies. The assay requires a short (less than 8 h) incubation in liquid media in the presence of a mitogen prior to plating in semisoft agar. Neither autologous serum, red cells, nor conditioned media are required to support colony formation. The kinetic and morphologic characteristics of T and B cell colonies were different. Formation of T cell macro- but not microcolonies was significantly impaired during aging. Formation of B cell colonies was decreased with aging, but the decrease was not significant.

Adult↗
PubMed1985

Naturally occurring human "antigalactosyl" IgG antibodies are heterophile antibodies recognizing blood-group-related substances.

IgG autoantibodies in human serum bind selectively to a new antigen that appears on senescent erythrocytes, thereby initiating their removal from the circulation. We tested the hypothesis that these IgG molecules recognize terminal galactose residues, thought by some investigators to become exposed as cells age. Results revealed that human antibodies with an "antigalactosyl" specificity are heterophile antibodies directed against rabbit and not human red cells. This was demonstrated using hemagglutination assays and immunoblotting. Immunoblots performed with affinity purified antigalactosyl antibodies revealed binding of the antibodies to rabbit, but not human, erythrocyte membrane proteins. They have a broad range of specificities including anti-B, anti-I, and possibly anti-P1 and Pk. These heterophile antibodies are not involved in the physiological removal of senescent human RBC by macrophages as indicated by the data demonstrating that incubation of senescent red cells aged in situ with galactose prior to incubation with macrophages does not alter their phagocytosis. Senescent cell IgG does not have an antigalactosyl specificity because IgG eluted from senescent cells aged in situ does not bind to rabbit red cells that have exposed alpha-galactosyl moieties.

Animals↗
PubMed1985

Senescent cell differentiation antigen.

A terminal differentiation antigen, the senescent cell antigen, appears on the surface of senescent and damaged cells. Appearance of this antigen initiates immunologic binding of physiologic IgG autoantibodies and removal of the cells by macrophages. The senescent cell antigen appears to be derived from band 3, the major anion transport protein of erythrocytes. Both the senescent cell antigen and band 3 have been demonstrated in the membranes of all cells examined.

Anion Exchange Protein 1, Erythrocyte↗
PubMed1984

Immunological aspects of aging: early changes in thymic activity.

Age related changes in immune function are preceded by changes in thymic function. One index of thymic function is the ability of the thymus to induce the differentiation of bone marrow pre-T cells into active T cells. Movement of precursors of PHA-responsive T cells into the thymus ceases prior to adolescence in long-lived, autoimmune disease resistant mice as determined by studies utilizing chromosome markers in parabiotic mice. The cause for this age-dependent, cell traffic phenomenon is not known, but it would appear that an extrathymic regulatory mechanism may be operating, since these precursor T cells have the capacity to migrate into the thymus, and even a grafted, involuting thymus is capable of accepting precursor T cells, under extraordinary conditions. Results indicate that shortly after adolescence, immature T cell precursors of PHA-responsive cells in the thymus, and perhaps the periphery, are the sole source of PHA-responsive T cells. T cell migration and maturation is discussed in relation to thymic hormones and the thymic-neuroendocrine regulatory axis.

Aging↗
PubMed1984

Localization of senescent cell antigen on band 3.

Senescent cell antigen is a glycosylated polypeptide, migrating in the band 4.5 region of NaDodSO4/polyacrylamide gels, that appears on the surface of senescent and damaged cells. Appearance of the senescent cell antigen initiates specific binding of IgG autoantibodies to it and the removal of erythrocytes (RBCs). Previous experiments suggested that the senescent cell antigen may be immunologically related to an integral membrane protein designated band 3 that is involved in anion transport across the RBC membrane. In the present studies, senescent cell antigen was mapped along the band 3 molecule by using topographically defined fragments of band 3. Both binding of IgG eluted from senescent RBCs ("senescent cell IgG") to defined proteolytic fragments of band 3 in immunoblots and two-dimensional peptide mapping of senescent cell antigen, band 3, and defined proteolytic fragments of band 3 were used to localize senescent cell antigen along the band 3 molecule. The data suggest that the antigenic determinants of the senescent cell antigen that are recognized by physiologic IgG autoantibodies reside on an external portion of a naturally occurring transmembrane fragment of band 3 that has lost a Mr approximately equal to 40,000 cytoplasmic (NH2-terminal) segment and part of the anion-transport region. A critical cell-age-specific cleavage of band 3 appears to occur in the transmembrane, anion-transport region of band 3.

Anion Exchange Protein 1, Erythrocyte↗
PubMed1984

IgG antibodies do not bind to band 3 in intact erythrocytes; enzymatic treatment of cells is required for IgG binding.

Naturally occurring autoantibodies to band 3 in normal human serum do not bind to red cells unless they are senescent, stored, or damaged. We suspected that IgG did not bind to native band 3 in intact red cells because of steric "shielding" of band 3 by adjacent molecules such as the glycophorins. In order to test this hypothesis, immunoelectron microscopy experiments were performed on intact red cells and red cells subjected to enzymatic treatment. Results revealed that antibodies to band 3 did not bind to untreated red cells, but did bind to red cells treated with trypsin, which spares band 3 but cleaves glycophorins A and C. Treatment with alpha-chymotrypsin did not significantly increase antiband 3 antibody binding. Binding of antibodies to the senescent cell antigen was not increased by either enzymatic treatment. It appears that binding of antibodies to the senescent cell antigen requires more than exposure of band 3 and proteolysis at a site other than the alpha-chymotrypsin sensitive site in intact red cells.

Autoantibodies↗