Papers by Joseph Cotropia
Immunization with chemically modified cancer cells. Abstr
Archives of Biochemistry and Biophysics, 1969
Surface proteins of human acute myelogenous leukemia (AML) cells
Surface immunoglobulins and protease inhibitors of human acute leukemia blasts
International Journal of Cancer, 1977
Cell‐surface proteins of human leukemic blasts were studied by direct immunofluorescence (DIF), l... more Cell‐surface proteins of human leukemic blasts were studied by direct immunofluorescence (DIF), low pH elution and immunodiffusion (ID). Among AML blasts from 21 patients, the average proportions of blasts positive for IgG, IgM, and IgA were 60%, 9%, and 9% respectively. In contrast, blasts from four CML patients in blast crisis and 14 ALL patients had surface IgG, IgM, and IgA values of 14%, 9%, and 7% respectively for the former group and 1.4%, 1.1%, and 0.8% respectively for the latter group. Blasts from 20 leukemic cell preparations were eluted at pH 2.4 for 30 min at 4° C in glycine. HC1 buffer. Immunodiffusion with appropriate specific antisera demonstrated intact IgG in 3 of 13 AML eluates. Ten of 13 AML eluates, 1 of 3 CML eluates, and 2 of 4 ALL eluates contained intact IgG and Fab fragment, but no Fc fragment. One CML eluate contained intact IgG; the remaining CML eluate contained Fab fragment only. Two ALL eluates contained no IgG or fragments by double diffusion. An eluate from a pool of normal human leukocytes from 20 normal donors contained intact IgG and Fc fragment, but no Fab fragment. Nineteen of 20 leukemic cell eluates also contained the anti‐proteases alpha‐1‐antitrypsin and alpha‐1‐anti‐chymotrypsin which were shown to have been proteolytically modified. Five of 20 leukemic cell eluates contained the anti‐protease alpha‐2‐macroglobulin. The normal leukocyte eluate contained alpha‐1‐anti‐trypsin but no alpha‐1‐anti‐chymotrypsin or alpha‐2‐macroglobulin. The presence of Fab fragment in AML, CML blast crisis and ALL eluates suggests IgG binding by Fab as antibody, while Fc fragment in normal leukocyte eluate suggests binding via Fc to the Fc receptor. The expression of cell‐associated proteolytic enzymes, as revealed by the presence of protease‐modified anti‐proteases, may explain cell‐surface IgG degradation. A consequence of surface proteolytic activity would be the degradation of IgG antibody to yield Fab fragment bound to membrane antigenic determinants. The Fab reaction product is incapable of interacting with either complement or Fc receptors. Therefore, such proteolytic activity may protect the leukemic blasts from lysis by complement‐dependent or antibody‐dependent cell‐mediated cytotoxic mechanisms.
Antigen Expression and Cell Surface Properties of Human Leukemic Blasts
Annals of the New York Academy of Sciences, 1976
It is well accepted that most human tumor cells express antigens that can evoke a cell-associated... more It is well accepted that most human tumor cells express antigens that can evoke a cell-associated and/or humoral immune response. Antitumor antibodies reacting with human tumor antigens have been demonstrated in the sera of cancer patients by a variety of in vitro techniques. A major factor in understanding the host-tumor relationship has been the recent demonstration that many tumor cells also appear to be coated in vivo with immunoglobulin, particularly IgG. Indeed, most human and animal tumor cells tested thus far have been found to be coated in vivo with immunoglobulin.R* 13* 45-64* 56-57 , in Although the immunoglobulins have been eluted from human and animal tumors 1.89 IS. by many investigators, the intactness and immunological reactivity of these immunoglobulins have not been clearly established. The immunoglobulin coat may consist of specific antitumor antibodies bound to their target antigens, o r may be 61-61. 69 or both. The biological role of bound immunoglobulin is unclear. Most of the data supported the concept that bound immunoglobulins may decrease immunogenicity or antigenicity of the coated cell. Indeed, allo-antibodies to tumors can block lymphocyte-mediated cytotoxicity in vitro6-7. l2 and acid-eluted IgG can enhance tumor growth in
Comparative studies of enzymes related to serine metabolism in fetal and adult liver
Biochimica et Biophysica Acta (BBA) - General Subjects, 1968
Abstract 1. 1. The levels of activity of D-glycerate dehydrogenase (D-glycerate: NAD (P)+ oxidore... more Abstract 1. 1. The levels of activity of D-glycerate dehydrogenase (D-glycerate: NAD (P)+ oxidoreductase) and phosphoglycerate dehydrogenase (D-3-phosphoglycerate: NAD+ oxidoreductase) have been determined in adult and fetal liver from rabbit, dog, ox, pig, cut, ...
Human monoclonal antibodies directed against the transmembrane glycoprotein (gp41) of HIV-1, and related peptides
Human monoclonal antibodies directed against the transmembrane glycoprotein (gp41) of human immunodeficiency virus-1 (HIV-1) and detection of antibodies against epitope (GCSGKLIC)
Human monoclonal antibodies directed against the transmembrane glycoprotein (gp41) of human immunodeficiency virus-1 (HIV-1)
Passive Immunotherapy against HIV-1
Infectious Agents and Pathogenesis
... 12. Alsmadi, O., Herz, R., Pinter, A., and Tilley, SA, 1997, A novel antibodydependent cellul... more ... 12. Alsmadi, O., Herz, R., Pinter, A., and Tilley, SA, 1997, A novel antibodydependent cellular cytotoxicity epitope in gp120 is identified by two monoclonal antibodies isolated from a long-term survivor of human immunodeficiency virus type 1 infection, J. Virol. 13. ...
A Human Monoclonal Antibody to HIV-1 gp41 with Neutralizing Activity Against Diverse Laboratory Isolates
Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology, 1996
ABSTRACT
The Journal of Infectious Diseases, 2004
Antimicrobial Agents and Chemotherapy, 2008
A-790742 is a potent human immunodeficiency virus type 1 (HIV-1) protease inhibitor, with 50% eff... more A-790742 is a potent human immunodeficiency virus type 1 (HIV-1) protease inhibitor, with 50% effective concentrations ranging from 2 to 7 nM against wild-type HIV-1. The activity of this compound is lowered by approximately sevenfold in the presence of 50% human serum. A-790742 maintained potent antiviral activity against lopinavir-resistant variants generated in vitro as well as against a panel of molecular clones containing proteases derived from HIV-1 patient isolates with multiple protease mutations. During in vitro selection, A-790742 selected two primary mutations (V82L and I84V) along with L23I, L33F, K45I, A71V/A, and V77I in the pNL4-3 background and two other mutations (A71V and V82G) accompanied by M46I and L63P in the HIV-1 RF background. HIV-1 pNL4-3 clones with a single V82L or I84V mutation were phenotypically resistant to A-790742 and ritonavir. Taking these results together, A-790742 displays a favorable anti-HIV-1 profile against both the wild type and a large num...
Cancer research, 1971
Although 6C3HED ascites lymphosarcoma grows lethally in C3H mice at low tumor cell inoculum, pote... more Although 6C3HED ascites lymphosarcoma grows lethally in C3H mice at low tumor cell inoculum, potent immune responses to this tumor have been elicited. It was selected as a model for studying the effectiveness of a number of chemical modifications of the tumor in eliciting immune responses of sufficient potency to protect the animal against a challenging lethal dose of the tumor cells. 6C3HED cells were modified by reactions with: (a) diazotized p-aminobenzoic acid, (b) fluorodinitrobenzene, (c) iodoacetamide, (d) iodoacetate, (e) yV-ethylmaleimide, and (/) p-hydroxymercuribenzoate. Cells modified with the strong antigenic determinants a and b failed to protect against IO6 6C3HED cells; c, d, and e protected fully;/gave partial protection. Alterations producing potent immunity involved blocking sulfhydryl groups with reagents not generally considered good haptens. lodoacetamide-treated EPF-1 lymphoma protected against an early transplant generation of EPF-1. No cytotoxic antibody to 6C3HED or EPF-1 in immune serum was demonstrable, but lymphoid cells from an immune C3H mouse protected a susceptible animal, indicating cell-mediated immunity.
Journal of Pediatric Orthopaedics, 1982
Injury, 1986
Eighty patients who had sustained a fracture of the tibial shaft were studied by scintigraphy usi... more Eighty patients who had sustained a fracture of the tibial shaft were studied by scintigraphy using technetium-99m labelled methylene diphosphonate (99Tcm MDP) and a gamma camera. Static scintigrams were obtained in the early stages following injury and examined for the presence of 'cold spots' which may indicate loss of blood supply to fracture fragments; these were found in 10 per cent of cases but did not bear any definite relationship to the normal progression of union. Sequential dynamic scintigrams were obtained at intervals up to 20 weeks after fracture to determine whether a pattern of uptake of tracer could be identified which correlated with the subsequent progression of union, but no significant difference was observed between fractures healing promptly (<20 weeks) and those in which healing was delayed (>20 weeks).
pages 4123 -4129 BUGGE ET AL 'Analysis of a highly immunodominant epitope in the Human Immunodefi... more pages 4123 -4129 BUGGE ET AL 'Analysis of a highly immunodominant epitope in the Human Immunodeficiency Virus type 1 transmembrane glycoprotein,gp41,defined by a human monoclonal antibody' • CHEMICAL ABSTRACTS, vol. 109, 1988, Columbus, Ohio, US; abstract no. 91111, ROSEN ET AL 'Synthetic HTLV-III peptides,compositions and kits containing them,and their use in immunoassays,immunization,and antibody production' page 547 ;column 2 ; • CHEMICAL ABSTRACTS, vol. 111, 1989, Columbus, Ohio, US; abstract no. 230559, NORRBY ET AL 'STLV-III (simian T-lymphotrophic virus type III)-related polypeptides,diagnostic systems,and assay methods' page 606 ;column 1 ; • J Inf Dis 156 (1987) 261-7 Remarks: The file contains technical information submitted after the application was filed and not included in this specification EP 0 492 560 B1 5 10 15 20 25 30 35 40 45 50 55 2
Passive Immunotherapy against HIV1
... 12. Alsmadi, O., Herz, R., Pinter, A., and Tilley, SA, 1997, A novel antibodydependent cellul... more ... 12. Alsmadi, O., Herz, R., Pinter, A., and Tilley, SA, 1997, A novel antibodydependent cellular cytotoxicity epitope in gp120 is identified by two monoclonal antibodies isolated from a long-term survivor of human immunodeficiency virus type 1 infection, J. Virol. 13. ...
Virology, 2000
A-790742 is a potent human immunodeficiency virus type 1 (HIV-1) protease inhibitor, with 50% eff... more A-790742 is a potent human immunodeficiency virus type 1 (HIV-1) protease inhibitor, with 50% effective concentrations ranging from 2 to 7 nM against wild-type HIV-1. The activity of this compound is lowered by approximately sevenfold in the presence of 50% human serum. A-790742 maintained potent antiviral activity against lopinavir-resistant variants generated in vitro as well as against a panel of molecular clones containing proteases derived from HIV-1 patient isolates with multiple protease mutations. During in vitro selection, A-790742 selected two primary mutations (V82L and I84V) along with L23I, L33F, K45I, A71V/A, and V77I in the pNL4-3 background and two other mutations (A71V and V82G) accompanied by M46I and L63P in the HIV-1 RF background. HIV-1 pNL4-3 clones with a single V82L or I84V mutation were phenotypically resistant to A-790742 and ritonavir. Taking these results together, A-790742 displays a favorable anti-HIV-1 profile against both the wild type and a large number of mutants resistant to other protease inhibitors. The selection of the uncommon V82L and V82G mutations in protease by A-790742 suggests the potential for an advantageous resistance profile with this protease inhibitor.
Uploads
Papers by Joseph Cotropia