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Biomedical subjects

T Mohanakumar

Publications and source records attributed to T Mohanakumar.

At least 271 records · Page 15Linked to original sources

Expression of a new cell surface antigen on activated murine macrophages.

A macrophage cell-surface antigen associated with pyran and Corynebacterium parvum-activated macrophages and P388D1 cells but not detectable on normal or glycogen and thioglycollate-elicited murine macrophages has been described. The antigen was demonstrated both by complement-mediated cytotoxicity and immunofluorescence, using an appropriately absorbed rabbit antiserum to P388D1. This antiserum should enable the characterization of activated macrophage cell populations on an individual cell basis and should be a useful probe to study the interactions of macrophages with tumor cells and the relationship of activation to cell-surface changes.

Animals↗

Persistent and fatal central-nervous-system ECHOvirus infections in patients with agammaglobulinemia.

We observed persistent ECHOvirus infection of the central nervous system, as defined by continued presence of isolatable virus in cerebrospinal fluid, in five patients with agammaglobulinemia. The immunologic deficit in each was characterized by absence of surface-immunoglobulin-bearing B lymphocytes and of lymph-node cortical follicles, but normal T-cell function. ECHOviruses 30, 19, 9 and 33 were recovered from cerebrospinal fluid for periods varying from two months to three years. The patients had few signs of acute central-nervous-system infection. Three of the five patients had a dermatomyositis-like syndrome, with peripheral lymphocytes that reacted with anti-human leukemia-specific primate and rabbit serums in a cytotoxicity assay. These data suggest that intact B-cell function is essential for eradication of ECHOvirus infection of the central nervous system.

Adult↗

Childhood lymphoblastic cancer: subgroups defined by nonhuman primate antisera to human lymphatic leukemia cell antigens.

Lymphoblasts from 23 children with acute lymphocytic leukemia (ALL) and 10 with lymphoblastic lymphoma (LBL) were studied by complement-dependent microcytoxicity tests with two nonhuman primate antisera defining leukemia-associated and lymphoma-associated antigens. Cells form 15 patients with ALL and 1 with LBL reacted only with antiserum to chronic lymphatic leukemia (CLL). These group-I patients were predominantly female. Most were pancytopenic and lacked mediastinal widening and T-cell markers; lymphoblasts from 15 were periodic acid-Schiff-positive. Cells from 8 male patients reacted only with antiserum to converted lymphosarcoma (LS). All these group-II patients expressed T-cell markers; 5 had mediastinal enlargement and 2, an abdominal mass. Six of the 8 were PAS-negative. Cells from 9 patients reacted with both antisera. The group-III patients demonstrated some characteristics of each of the above groups. Patients whose lymphoblasts reacted with CLL antiserum presented with clinical and laboratory features indicative of a good prognosis, i.e., ALL with PAS positivity and no T-cell markers or localized mass. Patients whose cells reacted with LS antiserum often had bad prognostic features: mediastinal or abdominal mass, expression of T-cell markers, and PAS negativity. These antisera appear able to differentiate childhood ALL from LBL. The distinction is important prognostically and perhaps therapeutically.

Adolescent↗

Serologic studies of the diagnosis and nosology of human leukemia.

Nonhuman primate antisera to human leukemia-associated antigens and to normal T- and B-lymphocyte antigens are useful reagents for detecting and classifying leukemic cells in a microcytotoxicity assay. These antisera are able to distinguish lymphocytic from myeloid leukemia cells, and can also identify acute myelomonocytic leukemia and chronic myelocytic leukemia blastic crisis cells from cells of other types of leukemia. The advantages and disadvantages of the reagents in the nosology and clinical management of leukemia patients are discussed in depth. However, despite certain shortcomings in the microcytotoxicity assays, the reagents and method do provide the necessary tools for antigenic isolation and identification. Purified antigen may then serve to open new horizons in the detection, diagnosis, classification and perhaps therapy of human leukemia.

Animals↗

Relationships between membrane antigens of human leukemic cells and oncogenic RNA virus structural components.

Leukemic cells from all human chronic granulocytic leukemia (CGL) and some acute myelomonocytic leukemia (AMML) donors are lysed by rabbit antisera to a purified glycoprotein of Friend murine leukemia virus (FLV gp71) in a microcytotoxicity assay. These antisera are not cytotoxic to cells from patients with acute myelocytic leukemia (AML), acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), or to peripheral blood lymphocytes from normal donors. A goat antiserum to gradient purified FLV in addition to reacting with cells from CGL and AMML donors also reacted with cells from AML patients and some ALL donors. However, this antiserum failed to react with cells from CLL patients. Peripheral blood and bone marrow leukocytes prepared from leukemic patients in clinical remission failed to react with antisera to FLV and FLV gp71. Absorption experiments demonstrated that the antigen on CGL cells which is reacting with the antiserum to FLV gp71 is also present on normal human platelets and neutrophils. Similar absorption studies showed that the antigen on AML cells detected by the FLV antiserum is not present on normal leukocytes and platelets and appears to be related to the major internal p30 antigens of mammalian RNA tumor viruses. Another antigenic relationship between oncornaviruses and membrane antigens of human leukemia cells was shown by the ability of FLV antigens to absorb the cytotoxic reactivity of nonhuman primate antisera detecting human leukemia-associated antigens. FLV and FLV gp71 antigens were able to absorb all cytotoxic activity of monkey and chimpanzee antisera to human myeloid leukemia antigens when these antisera were tested with CGL cells. These two approaches to an analysis of cross-reactivity indicate that the antigenic determinant(s) detected by the cytotoxic reactions of the FLV gp71 antiserum with human CGL cells is different from the determinant on FLV gp71 which is responsible for the inhibition of the reactivity of simian antisera with CGL cells. Since the goat and rabbit antisera to FLV and FLV gp71 are able to distinguish AML from CGL cells by direct cytotoxicity testing and absorption, they may be valuable reagents for the serological diagnosis of myeloid leukemia. In addition, since peripheral blood cells from AML and CGL patients in clinical remission were seronegative, the antisera may be valuable as management aids. The data in this report indicates that whatever the mechanism of leukemogenesis is in man, cells from CGL and AML patients possess certain membrane antigens which cross-react with FLV structural components such as p30 and gp71.

Antigens, Neoplasm↗

The use of non-human primates for production of antisera to human tumor-associated antigens.

High-titered antisera against human melanoma- and leukemia-associated antigens have been produced in non-human primates. The data from this and from other studies suggest that this model may prove a valuable source of highly specific antisera against a variety of human tumor-associated antigens or alloantigens. Our methods for production and characterization of these antisera are reported.

Animals↗

Human acute myelomonocytic leukemia: serologic studies with simian antisera.

Simian antisera to human leukemia cells were able to distinguish antigens specific for lymphocytic types of leukemia from those expressed on certain myeloid leukemia cells. In this investigation, cells from acute myelomonocytic leukemia patients (AMML) were examined for their membrane-associated leukemia antigens. Simian antisera to both lymphocytic and myelogenous leukemia cells lysed cells from AMML donors. Monkey antisera to AMML cells, by direct microcytotoxicity testing, were cytotoxic for cells from all AMML patients, as well as for cells of certain patients with myeloid leukemia. Cells from patients with lymphatic leukemia were nonreactive. However, absorption studies indicated an antigen present on cells from patients with chronic lymphocytic leukemia which cross-reacted with AMML cell antigens. Sequential analyses of the serologic reactivity of cells from AMML patients undergoing chemotherapy corresponded with the clinical course of the patient, even though there was little correlation between the percentage of blast cells present and the per cent cytotoxicity with the antisera. At certain times a higher percentage of seropositive cells could be detected over that seen on morphological evaluation. The estimation of leukemic cells by serologic means could aid in the diagnosis and management of AMML patients during chemotherapy.

Animals↗

Membrane-bound immunoglobulins on human leukemic cells. Evidence for humoral immune responses of patients to leukemia-associated antigens.

Immunoglobulins were detected on the membranes of human leukemic cells by a microcytotoxicity technique. A significant percentage of lymphocytes from normal donors failed to react with goat antisera to human heavy chain determinants or to lambda-light chains. Lymphocytes from some normal donors, however, did react with antisera to k-light chains. A high percentage (50-90) of cells from some leukemia patients were killed by antisera to light chains and by one or more antisera to heavy chain determinants. Trypsin treatment of leukemic cells resulted in a loss of cytotoxic activity with all immunoglobulin antisera. Reactivity with the k-light chain antiserum was detectable 2 h after trypsinization of chronic myeloid leukemic (CML) cells and 8 h after treatment of acute lymphocytic leukemic (ALL) cells. Reactivity with the antisera to heavy chain determinants and lambda-light chains could not be detected 8 and 48 h after trypsinization of CML and ALL cells, respectively. The cytotoxic activity of the immunoglobulin antisera to heavy chains was abolished by absorption with the specific immunoglobulin used to define the antisera by precipitation. Eluates (pH 3.2) prepared from leukemic cells which reacted by cytotoxicity with the immunoglobulin antisera were shown to contain immunoglobulins of different heavy chain classes. In addition, some of the eluates had cytotoxic antibody activity to human leukemia cells. The specificity of the eluted antibodies is similar to the specificity previously described for cytophilic antibodies from leukemic patients and nonhuman primate antisera to human leukemia cells. The possible in vitro detection and in vivo significance of the eluted non-complement-fixing antibodies is considered.

Cytotoxicity Tests, Immunologic↗

Human leukemia-associated antigens: detection on cells of established lymphoblastoid lines.

Primate and rabbit antisera to different morphologic classes of human leukemia cells, after appropriate absorptions, detected leukemia-associated antigens present on cultured lymphoblastoid cell lines derived from leukemia patients. The primate antisera distinguished antigens on cells derived from myeloid leukemia patients from those on cells derived from lymphocytic leukemia patients. Of particular interest was the fact that antigens of myeloid leukemia, but not of lymphatic leukemia, were detected on lymphoid cell lines established from blood of patients with myeloid leukemia. One of four lymphoblastoid cell lines derived from normal donors expressed antigens of lymphatic leukemia. Leukemia-associated antigens were not found on the HRIK lymphoblastoid line derived from a Burkitt's lymphoma patient on skin fibroblasts or HeLa cells. Expression of these antigens on cultured cells derived from leukemia patients could not be related to the presence of the EB virus or the EB virus genome. Rabbit antisera detected antigens common to cells from patients with myeloid and lymphocytic leukemia. Absorption experiments demonstrated that the antigens detected on cell lines derived from leukemia patients are similar to those detected by the primate and rabbit antisera on fresh peripheral blood leukemic cells. The serologic detection of leukemia-associated antigens on lymphoblastoid cell lines indicates that some of these cultures contain cells with antigenic properties similar to those of human peripheral blood leukemic cells.

Animals↗

Human melanoma and leukemia associated antigens difined by nonhuman primate antisera.

The rationale of our approach to the detection and characterization of human leukemia and melanoma associated membrane antigens is to take advantage of the unique immunological recognition perspective of simians to huamn antigens. There are enough antigenic similarities between man and nonhuman primates to blunt the immune response of apes and monkeys to huamn species-specific antigens. Their response to allogeneic normal human antigens such as HL-A can now be managed by in vitro absorption procedures. High titered antibodies specific for tumor associated membrane antigens have not been well documented in serological studies with patients' sera. Immunization of nonhuman primates utilizes a fully immunocompetent recipient who has no tumor and is not on chemotherapy. The immunization can utilize adjuvants and other regimens that morally and ethically cannot be easily used for human allogeneic immunization. The simian antisera that are shown to be specific for human tumor membrane antigens can then be utilized for studies on the isolation and characterization of the antigens. Similar studies with HL-A antigens indicated that the solubilized partially purified antigens can then be used to elicit high titered antibodies in other simians. These latter antisera can then be used for more sensitive assays and studies on the association of the antigen(s) with the cell membrane. Although the work summarized here covers leukemia and melamona antigens, it is felt the approach will serve as a model for the detection by simian antisera of tumor-specific membrane antigens of cancer cells from patients with various types of solid tumors.

Animals↗

Antigens specific for human lymphocytic and myeloid leukemia cells: detection by nonhuman primate antiserums.

Primate antiserums to human leukemia cells can detect antigens specific for lymphocytic leukemia cells or antigens present on certain myeloid leukemia cells. The antigen specific for lymphocytic leukemia cells is destroyed by treatment with neuraminidase or trypsin. Tryptic digests of lymphocytic leukemia cells contain the antigen, which has a high molecular weight.

Agglutination Tests↗