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Biomedical subjects

J Dilley

Publications and source records attributed to J Dilley.

33 records · Page 2Linked to original sources
PubMed1981

Studies of a human T lymphocyte antigen recognized by a monoclonal antibody.

A monoclonal antibody (designated L17F12) detects an antigen present on 95-100% of human peripheral T lymphocytes, the majority of thymocytes, and acute lymphocytic leukemia T cells but not B cells, B-cell lines, or monocytes. Examination of frozen tissue sections by the immunoperoxidase method revealed that the cells expressing this antigen were found predominantly in the medulla of thymus and in T-cell zones of lymph node and spleen. The antigen recognized by L17F12 was associated with a cell-surface glycoprotein of 67,000 daltons. L17F12 was used to isolate this molecule from human thymocytes, normal peripheral T cells, leukemic T cells, and T-cell lines. Expression of this antigen on normal T cells was not diminished by prolonged exposure in vitro to various T-cell stimuli. In the absence of complement, L17F12 bound to T cells without altering proliferative functions, thus enabling rapid purification of functionally intact T cells. In the presence of complement, L17F12 was cytolytic for T cells, providing the basis for depletion of T cells from heterogeneous populations. These data suggest that the monoclonal antibody L17F12 recognizes a specific T-cell differentiation protein. This antibody will be useful in studies of the human immune system.

Animals↗
PubMed1981

Definition of the high-risk acute lymphoblastic leukemia patient by immunological phenotyping with monoclonal antibodies.

An accurate method of classification of the surface membrane characteristics of blast cells from patients with acute lymphoblastic leukemia would allow a more definitive study of the nature of this disease. Monoclonal antibodies have been produced to the surface antigens of leukemic blasts form a patient with high-risk acute lymphoblastic leukemia. Two antibodies of interest were obtained from this immunization. These two, in combination with a monoclonal antibody with anti-Ia specificity, have been used to obtain surface phenotypes for patients with childhood acute lymphoblastic leukemia. Preliminary results indicate that the definition of a high-risk group, using these antibodies, possible.

Acute Disease↗
PubMed1980

Inhibition of lymphoma hybrids by human interferon.

A set of stable mouse-human hybrids was constructed from the neoplastic lymphocytes from a patient with nodular lymphoma and from another with chronic lymphocytic leukaemia. Both patients had shown a clinical response to human leucocyte interferon. The same interferon preparation inhibited the growth rate of 14 out of 17 established hybrid cell lines. This system provides evidence of a direct growth inhibitory effect of interferon on neoplastic B lymphocytes. Such a system could be used to predict the sensitivity of a patient's tumour before therapy.

Aged↗
PubMed1980

Immunologic phenotype in 30 patients with diffuse large-cell lymphoma.

Frozen sections of 30 diffuse large-cell ("histiocytic") lymphomas that had arisen in both nodal and extranodal sites were stained with immunoglobulin light-chain and heavy-chain reagents, with nonoclonal antibodies to THAT HAD ARISEN IN BOTH NODAL AND EXTRANODAL SITES WERE STAINED WITH IMMUNOGLOBULIN LIGHT-CHAIN AND HEAVY-CHAIN REAGENTS, WITH MONOCLONAL ANTIBODIES TO T and B-cell antigens, and with an esterase marker for macrophages. Fourteen lymphomas expressed immunoglobulin light chains and were shown to be monoclonal; F(ab')2 fragments were sometimes necessary to demonstrate their monoclonal nature. Mu (IgM) was the most frequently expressed heavy chain, but in many patients other heavy chains were found. None of the lymphomas stained with T-cell antibodies or the esterase; 15 did not stain for immunoglobulin, but 13 of these 15 did express Ia antigen. These immunologic markers identified eight different phenotypes. Retrospective clinical analysis of the patients suggested that those who were immunoglobulin-positive had more advanced disease and shorter survival, but confirmation of the clinical relevance of immunologic phenotype will require prospective studies.

Adult↗
PubMed1980

Immunoglobulin secretion by mouse X human hybridomas: an approach for the production of anti-idiotype reagents useful in monitoring patients with B cell lymphoma.

Tumor cells were obtained from a patient with nodular lymphoma, a monoclonal B cell malignancy. These non-Ig-secreting lymphoma cells were hybridized to mouse myeloma cells. Hybridomas secreting human Ig were obtained in high frequency. One clone, which was a stable producer of human heavy and light chains, but which had lost production of mouse light chains, was chosen for study. It secreted a human IgM pentamer. The Ig produced by this clone was purified and used as an immunogen for the production of anti-idiotype antibodies. These antibodies recognized the specific cell surface Ig of the lymphoma cells and have been used to detect idiotype-bearing cells in the blood of the original patient, even at times when the disease was in clinical remission. Moreover, free idiotype could be detected in the patient's serum. Both the levels of Id+ cells and free idiotype correlated with disease activity, rising in relapse and falling in remission.

Animals↗
PubMed1979

A human thymus-leukemia antigen defined by hybridoma monoclonal antibodies.

A series of mouse hybridomas producing monoclonal antibodies against human acute lymphocytic leukemia (ALL) cells was generated and screened for tumor specificity. Among 1200 primary cultures, 60 produced an antibody that could distinguish between the immunizing leukemia cells and an isologous B lymphoblastoid cell line. Of these, two produced an antibody that detects an antigen expressed preferentially on ALL cells and on a subpopulation of normal cells found in the cortex of the thymus. Other normal human lymphoid cells from lymph nodes, spleen, bone marrow, and peripheral blood express only low levels of this antigen. High levels of this "thymus-leukemia" antigen were found on T-ALL cells, T-ALL-derived cell lines, and some "null" ALL cells. By contrast, B-cell leukemias, B lymphoblastoid cell lines, and normal and malignant myeloid cells contain either low or undetectable amounts of this antigen. The thymus-leukemia antigen has been isolated from the membranes of leukemia cells by detergent solubilization and subsequent immunoprecipitation with the monoclonal antibody. Preliminary biochemical characterization shows the antigen to be associated with a polypeptide of Mr approximately 28,000.

Antibody Specificity↗
PubMed1978

Rescue of immunoglobulin secretion from human neoplastic lymphoid cells by somatic cell hybridization.

B leukemia cells from four different patients were hybridized with a mouse myeloma cell line with polyethylene glycol as a fusing agent. The original leukemia cells all expressed immunoglobulin on their surface, but failed to secrete it. Over 200 different human-mouse somatic cell hybrids were obtained; 57% of them secreted human immunoglobulin in large amounts. Human immunoglobulin secretion can be a stable property of these hybrid cells over months of continuous culture. In each case the human immunoglobulin secreted was restricted to the light chain type expressed by the parental B leukemia cell. In addition, these hybrid cells secreted the original mouse myeloma protein and a variety of mixed human-mouse immunoglobulin molecules.

Animals↗
PubMed1977

The in vitro antibody response to cell surface antigens. I. The xenogeneic response to human leukemia cells.

An in vitro spleen fragment culture system has been developed for the production and analysis of xenogeneic antibody responses to cell surface antigens. Depending on the methods of immunization and in vitro stimulation employed, mouse spleen fragments can produce antibody of both IgG and IgM classes directed against human cell surface antigens for more than 30 days in culture. A saturation binding analysis of the antibody products indicates that their range of specificities was more restricted than that of serum antibody. Approximately 5% of the in vitro antibody products raised against a homogeneous population of human leukemia cells could distinguish between the antigens present on the leukemia cells and those present on normal human lymphocytes. Methods previously employed to influence the range of serum antibodies expressed against complex immunogens, such as suppression of certain responses by passive administration of antibody at the time of immunization, were tested in the in vitro spleen culture system and resulted in successful modulation of the antibody response patterns observed.

Animals↗
PubMed1977

The in vitro antibody response to cell surface antigens. II. Monoclonal antibodies to human leukemia cells.

A method has been developed for the production of monoclonal mouse antibody responses in vitro against human cell surface antigens. Limiting numbers of immune spleen cells were transferred to syngeneic, irradiated recipients whose spleen fragments were then cultured in vitro and stimulated to produce antibody. The majority of the antibody from any one fragment culture was likely to be the product of a single donor B cell and thus monoclonal. Evidence for this included a linear relationship between donor cell transferred and spleen fragments producing antibody, extremely restricted isoelectric focusing patterns of the individual antibody products, and unique reactivity patterns of these antibodies against a panel of human lymphoid cells. Different human B leukemia cells were seen as immunogenically distinct by the mouse. By using the monoclonal mouse antibodies as probes, a fine analysis of cell surface antigens is jow possible.

Animals↗
PubMed1973

Maturation of B lymphocytes in the rat. I. Migration pattern, tissue distribution, and turnover rate of unprimed and primed B lymphocytes involved in the adoptive antidinitrophenyl response.

The migration pattern, tissue distribution, and turnover rate of unprimed and primed B lymphocytes involved in the adoptive anti-DNP response was studied. The adoptive primary response restored by unprimed spleen or thoracic duct cells passaged through an intermediate host (intravenous injection and subsequent collection in the thoracic duct lymph) was markedly diminished as compared with that restored by unpassaged cells. On the other hand, the adoptive response restored by passaged spleen or thoracic duct cells from DNP-primed donors was greater than or the same as that restored with unpassaged cells, respectively. This suggests that unprimed B cells change from nonrecirculating to recirculating lymphocytes after exposure to antigen. Studies of the adoptive anti-DNP response restored by unprimed or primed bone marrow cells showed little change in the time-course or amplitude of the response restored by either population of cells. The relative inability of marrow cells to carry immunological memory was related to the inability of recirculating memory cells to penetrate the marrow. The turnover rate of unprimed and primed B cells was investigated by treating the cell donors with [(3)H]thymidine for 48 h before removal of thoracic duct or spleen cells. The adoptive anti-DNP response restored by unprimed or primed cells was not affected by [(3)H]thymidine treatment. This indicates that both populations of cells turn over slowly. However, our previous studies show that unprimed B cells involved in the adoptive antibody response to ferritin turn over rapidly. The different findings are discussed in the context of antigen-dependent B-cell maturation.

Animals↗
PubMed1973

Biological characteristics of T and B memory lymphocytes in the rat.

The adoptive secondary antibody response of rats to the hapten-protein conjugate dinitrophenyl-diphtheria toxoid (DNP-DT) was used to investigate the migratory properties and rate of formation of T and B memory cells in the spleen. The experimental findings show that hapten (DNP-BSA)- and carrier (DT)-primed spleen cells act synergistically in the restoration of the adoptive anti-DNP response. Passage of both hapten- and carrier-primed spleen cells through an intermediate host (intravenous injection and subsequent collection in the thoracic duct lymph) showed that both cell types are able to recirculate from the blood to the lymph. In addition, memory to the hapten or carrier could be withdrawn from the spleen by prolonged thoracic duct drainage. The rate of formation of hapten- and carrier-primed spleen cells was studied by treating donors with [(3)H]thymidine for 48 h before cell transfer in an attempt to "suicide" rapidly dividing cells. Only a slight reduction in the adoptive response to the hapten or carrier was noted upon transfer of treated cells to irradiated hosts. In further experiments, the cell lineage of hapten- and carrier-primed cells was determined by treating each cell type in vitro with rabbit antirat B cell serum (RARBS) and complement. Although treatment with RARBS did not affect the adoptive response restored by carrier-primed cells, the same treatment abolished the response restored by hapten-primed cells. These findings indicate that T and B memory cells in the spleen of the rat are relatively long-lived, recirculating lymphocytes. The contribution of fixed or rapidly turning over cells to immunological memory is small or negligible as compared with the latter cells.

Animals↗
PubMedDate not supplied

Gamma imaging of atherosclerotic lesions: the role of antibody affinity in in vivo target localization.

BACKGROUND: Monoclonal antibodies are attractive agents for noninvasive localization of various cardiovascular disorders. Because proliferating intimal smooth muscle cells are important components of atherosclerotic lesions, radiolabeled antibody Z2D3 specific for proliferating smooth muscle cells has been used for immunoscintigraphic localization of experimental atherosclerotic lesions. This study was undertaken to assess the role of antibody affinity in optimization of immunoscintigraphic localization of these lesions. Z2D3 belongs to the immunoglobulin (Ig) M class of antibodies. For immunoscintigraphic studies, attempts were made to prepare F(ab')2 or Fab fragments from the parent cell line. Fragmentation of Z2D3-IgM or its two subclones (B7 and 2B12) was not possible; therefore the parent hybridoma line was subjected to class switching. Cell lines 5C5 and 3E5 secreted antibody of the IgG1 subclass. The Z2D3-IgG1 antibodies were enzymatically digested to provide F(ab')2. Because of a tenfold loss of immunoreactivity of these class-switched antibodies, the parent clone was subsequently genetically engineered to obtain a mouse/human chimeric antibody with human IgG1 constant region. F(ab')2 of Z2D3-73.30 chimeric antibody retained the immunoreactivity relative to the original Z2D3-IgM. Radiolabeled murine and chimeric F(ab')2 fragments were used to assess the role of affinity in gamma scintigraphic visualization of experimental atherosclerotic lesions. METHODS AND RESULTS: Experimental atherosclerotic lesions were induced in 19 rabbits by abdominal aortic balloon deendothelialization followed by a hyperlipidemic diet for 12 weeks. 111In-labeled chimeric high-affinity Z2D3 F(ab')2 fragments (111In-Hi.aff Z2D3) were administered in four animals. Uptake was compared with 111In-labeled F(ab')2 of nonspecific human IgG1 (n = 4), murine low-affinity Z2D3-5C5 (111In-Lo.aff Z2D3; n = 4), nonspecific murine IgG1 monoclonal antibodies (n = 4), and 123I-labeled murine low-affinity Z2D3-3E5 (n = 3). Atherosclerotic lesions were visualized 48 hours after administration of the chimeric Hi.aff-Z2D3 antibody in all animals. Lesions were not visualized in rabbits injected with Lo.aff-Z2D3 or murine or human nonspecific antibodies. Mean percent injected dose per gram in the lesion was significantly higher with the 111In-Hi.aff-Z2D3 (0.112% +/- 0.024%) compared with 111In-Lo.aff-Z2D3 (0.037% +/- 0.005%; p = 0.03), human nonspecific (0.027% +/- 0.004%; p = 0.01), or murine nonspecific antibodies (0.006% +/- 0.001%; p = 0.0004). Nonspecific activity in unballooned thoracic aortic segments (normal) was comparable in the 111In-Hi.aff-Z2D3 (0.019 +/- 0.003) and the 111In-Lo.aff-Z2D3 (0.011% +/- 0.005%; p = 0.3) antibodies. The lesion activities of the Lo.aff-Z2D3 labeled with 111In (0.037 +/- 0.005) or 123I (0.034 +/- 0.007; p = 0.71) were similar regardless of the radioisotopes used for labeling. CONCLUSIONS: Our study demonstrates that the specificity of an antibody for the target antigen in the atheroma is a necessary condition for in vivo targeting. However, high enough affinity of an antibody is an essential component for noninvasive diagnostic visualization of experimental atherosclerotic lesions.

Animals↗
PubMedDate not supplied

Toxicity studies with decamethrin, a synthetic pyrethroid insecticide.

Decamethrin is a synthetic pyrethroid insecticide that has been under investigation by the World Health Organization for use in some vector control programs. Decamethrin proved to be a highly toxic pyrethroid ester. The acute LD50 for adult female rats was 31 mg/kg by the oral route and 4 mg/kg by the intravenous route of administration. The LD50 was observed to be sex and age dependent, with higher values recorded for weanlings and males. Initial signs of decamethrin poisoning include profuse salivation and convulsive movements. Weakness, dyspnea, anorexia and staining of the fur were observed beyond the first day following compound administration. Absorption of decamethrin was rapid by the inhalation route and minimal by the dermal route of administration. No evidence of teratogenic activity was found in rats or mice at dose levels that produced marked maternal toxicity, and no persistent toxicity was observed in neonatal rats that received perinatal exposure to decamethrin. No mutagenic activity was detected in three different in vitro assays, with or without metabolic activation.

Aerosols↗