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Biomedical subjects

I Royston

Publications and source records attributed to I Royston.

At least 73 records · Page 4Linked to original sources
PubMed1983

A novel cell surface antigen (T305) found in increased frequency on acute leukemia cells and in autoimmune disease states.

Monoclonal antibody T305, prepared by immunizing mice with the T-ALL derived cell line RPMI-8402, immunoprecipitates a single chain glycoprotein with m.w. 160,000 daltons (under reducing conditions) or 180,000 daltons (under nonreducing conditions). In immunofluorescence assays, antibody T305 reacted with a subpopulation of T cells in normal blood (22 +/- 6%), thymus (28 +/- 11%), and lymph node (24 +/- 6%). Increased frequency of T cells reactive with antibody T305 was found in peripheral blood of patients with infectious mononucleosis (greater than 80%), graft-vs-host disease after bone marrow transplantation (65 +/- 11%), acquired immunodeficiency syndrome (53 +/- 12%). The T cells in synovial fluid of patients with rheumatoid arthritis had increased frequency of antibody T305 reactive cells (59 +/- 8%) as compared to their peripheral blood (18 +/- 7%). Two color immunofluorescent studies demonstrated that the T305+ T cells predominantly co-stained with antibody Leu 2a (suppressor/cytotoxic subset) in both normals and disease state blood. After cell sorting to obtain T305+ and T305- subpopulations, we demonstrated that a) natural killer and antibody-dependent cellular cytotoxicity activity in normal blood was in the T305+ but not T305- T cells; b) cytotoxic T cells induced by mixed lymphocyte reaction were predominantly T305+; c) T305- T cells could be induced in vitro to express T305 antigen by mitogens or allogeneic B cells; d) the DNA content of T305+ and T305- T cells in normal blood was similar (greater 95% of cells with G0/G1 level); e) after mitogen stimulation, T305 antigen induction on previously T305- cells occurs before S-phase; and f) significantly more [3H]-thymidine after mitogen stimulation was incorporated by originally T305- cells than by originally T305+ cells (p less than 0.001). The T305 antigen was not restricted to T cells because it was also found on myeloid precursors in bone marrow but was not present on polymorphonuclear leukocytes, red blood cells, platelets, muscle, liver, skin, kidney, lung, or brain. Antibody T305 was found on 24/25 cases of acute leukemia (6 T-ALL, 10/11 cALL, 7 AML, and 1 AMOL) but not on 18 cases of chronic leukemia (B-CLL, T-CLL, null CLL, CML). The importance of the T305 antigen is that it is present on a high number of T cells in certain autoimmune diseases and on virtually all acute leukemia cells. Its distribution on immature and in vitro activated cells suggests that it may represent a receptor for signals related to cellular replication or differentiation.

Animals↗
PubMed1982

Development of a rapid microELISA assay for screening hybridoma supernatants for murine monoclonal antibodies.

A micro enzyme-linked immunosorbent assay (ELISA) utilizing a filtration method has been developed which allows the rapid, simple, and sensitive detection of monoclonal antibodies that recognize either soluble or cell surface antigens. This assay involves the immobilization of target cells (or soluble antigen) onto glass fiber filter discs followed by an incubation with the test hybridoma supernatant and subsequent analysis by ELISA. A specially designed 96-well filtration device is employed which serves both as an incubation chamber and as a filtration manifold. This microELISA requires small volumes of antiserum, few target cells, and can be completed in less than 2 h. This assay is well suited for the rapid screening of murine hybridoma supernatants and can be adapted to detect monoclonal antibodies from other species.

Animals↗
PubMed1982

Extensive disease small cell carcinoma of the lung: trial of non-cross resistant chemotherapy and consolidation radiotherapy.

Twenty-nine patients with extensive disease, small-cell carcinoma of the lung, were treated with two cycles of intensive combination chemotherapy: HexaVAC (hexamethylmelamine, vincristine, Adriamycin, cyclophosphamide). Responders received prophylactic cranial radiation (2000 rad/10 fractions) and non cross resistant chemotherapy via a schedule of alternating cycles of CMV (cyclophosphamide, methotrexate, VP-16-213) and AMV (Adriamycin, methotrexate, VP-16-213). Whenever a complete response was achieved, consolidation radiotherapy was given to the lung primary (4000 rad/20 fractions, split dose) and abdominal metastases (2000 rad/10 fractions) synchronous with CMV therapy. The complete response rate was 14% with HexaVAC, but increased to 38% during CMV/AMV. Total response rate (complete and partial) was 59% and median survival was 42 weeks. Prophylactic brain radiation prevented clinical relapse in the brain in all 14 patients who received it. However, consolidation radiotherapy failed to prevent clinical relapse in the lung and/or liver, and therapeutic brain radiation (3000 rad) failed to prevent relapse in that site. The simultaneous administration of radiotherapy and chemotherapy was well-tolerated although two patients with poor performance status died of infectious complications while leukopenic. In spite of the high response rate, durable remissions with prolonged disease free survival were rare. Further evaluation of induction, consolidation, and maintenance modes of therapy are indicated.

Adult↗
PubMed1982

Human autologous mixed lymphocyte reactivity is primarily specific for xenoprotein determinants adsorbed to antigen-presenting cells during rosette formation with sheep erythrocytes.

We present evidence that most T cells proliferating in response to autologous sheep erythrocyte (SRBC)-separated non-T cells (NT) cells are not specific for autoantigens but for antigens derived from xenogeneic sources. The conclusion was based on the following three observations. First, we found that NT cells isolated in the absence of xenoproteins by means of density gradient centrifugation on Percoll only weakly stimulated autologous T cells. Because this weak proliferation could not be expanded in restimulation experiments, its significance as an immune recognitive event remains questionable. NT cells isolated by the above method in the absence of xenogeneic determinants readily acquired stimulatory capacity after brief exposure to either SRBC or fetal calf serum. Second, restimulation of T memory cells generated in 1 degree autologous mixed lymphocyte reaction (AMLR) against SRBC-separated autologous NT cells was exclusively seen when NT cells exposed to or separated with xenoproteins were used for restimulation. Third, T memory cells generated against SRBC-separated autologous NT cells were specifically restimulated by autologous Percoll-separated NT cells that had been pulsed with a variety of xenogeneic mammalian sera. These xenogeneic determinants were preferentially recognized in context with autologous HLA-DR+ cells. From these findings and from our previous results that indicated an absolute requirement of HLA-DR+-adherent NT cells (8), we conclude that human AMLR primarily does not represent an autoantigen but a xenoantigen response that is genetically restricted by the HLA-DR type of the antigen-presenting cell.

Animals↗
PubMed1982

Colony-forming assay for circulating chronic lymphocytic leukemia cells.

In these studies, we report adaptation of a colony-forming assay to chronic lymphocytic leukemia (CLL) peripheral blood cells. T-lymphocyte-depleted CLL peripheral blood cells were cultured with irradiated, normal T cells and media conditioned by normal, mitogen-stimulated T cells in methylcellulose. Colonies containing small and transformed lymphocytes appeared after 5-7 days incubation. The plating efficiency of CLL colonies was 0.15 +/- 0.08% (x +/- S.D.), similar to that of other colony-forming systems. The majority of CLL colony-forming cells were in S phase (50 +/- 4% x +/- S.E.) as determined by thymidine suicide and the fraction of colony-forming cells in S phase was inversely related to the WBC. Cells harvested from CLL colonies lacked surface markers for T lymphocytes and stained positively for monoclonal surface and/or cytoplasmic immunoglobulin light chains. A 1-h incubation was used to study the in vitro response of CLL colony-forming cells to adriamycin and melphalan. Preliminary studies suggest differences in patterns of in vitro sensitivity to melphalan between patients previously treated with alkylating agents and those who had not received treatment. This system can be used to study regulation of CLL cell proliferation, and may have utility in predicting response to chemotherapeutic agents.

Cell Division↗
PubMed1982

Membrane antigen on Epstein--Barr virus-infected human B cells recognized by a monoclonal antibody.

This paper describes a monoclonal antibody (B532) that detects a membrane antigen present on greater than or equal to 95% of the B cells from lines carrying the Epstein-Barr virus (EBV) genome. Evidence suggesting that B532 is EBV-related was originally obtained by using a cell-binding radioassay with different cell line substrates. Immunofluorescence and cell-sorter analysis confirmed that the antigen was present in high density on all EBV-infected lymphoblastoid B-cell lines, but not on EBV-negative B-, T-, myeloid, or null cell lines. Isolated normal peripheral blood B and T lymphocytes and monocytes failed to bind B532. The monoclonal antibody did not inhibit in vitro EVB infection nor did it block the killing of EBV-infected targets by cytotoxic T lymphocytes. The cell surface antigen recognized by B532 was shown by immunoprecipitation to have a molecular weight of approximately 45,000.

Animals↗
PubMed1982

Utility of monoclonal antibodies in the immunologic phenotyping of acute lymphoblastic leukemia.

Peripheral blood and/or bone marrow lymphoblasts from 34 children and 11 adults with acute lymphoblastic leukemia (ALL) were evaluated with a monoclonal anti-Ia antibody and a monoclonal anti-pan T-cell antibody (T101) specific for a 65,000-dalton T-cell antigen (T65). Seventy-six per cent of cases were Ia+T65-, 20% were Ia-T65+ and the remaining 4% were Ia-T65-. Anti-Ia and T101 reactivity were mutually exclusive and no Ia+T65+ cases were identified. In childhood ALL, the Ia+T65- phenotype was associated with good prognostic factors and longer median disease-free survival than Ia-T65+ patients whose clinical parameters resembled those characteristic of high-risk T-cell ALL. Included in the Ia-T65+ group were three E-rosette negative cases with clinical features of T-cell disease. Our findings compare favorably with the results of other investigators utilizing polyclonal antisera and suggest that these monoclonal antibodies, which offer the advantages of monospecific standardized reagents, will prove useful in the immunologic characterization of ALL.

Adolescent↗
PubMed1982

Establishment and characterization of an Epstein-Barr virus-negative lymphoma B-cell from a patient with a diffuse large cell lymphoma.

Cell line (LNPL) was established from a tumor biopsy of a nasopharyngeal "histiocytic" lymphoma composed of large noncleaved B-cells. LNPL expressed immunoglobulin M kappa surface immunoglobulin, as did the original tumor. LNPL also expressed Ia antigen but lacked Epstein-Barr virus nuclear antigen. It exhibited a translocation between chromosomes 8 and 14 which has been described in certain other malignant lymphoproliferative disorders. An autologous T-cell line lacked the translocation between chromosomes 8 and 14. LNPL is being used as an immunogen to produce monoclonal antibodies in our laboratory. Such cell lines may facilitate identification of lymphoma-associated surface antigens.

Adolescent↗
PubMed1982

Non-cross-resistant chemotherapy and consolidation radiotherapy for small cell carcinoma of the lung.

Fifty-six patients with small cell carcinoma of the lung were treated with a two-cyclic induction course of hexamethylmelamine, vincristine, doxorubicin, and cyclophosphamide. Patients with limited disease (LD) who responded and patients with extensive disease (ED) who had a complete response received prophylactic whole-brain radiotherapy, as well as radiotherapy to thoracic and abdominal sites of disease. Concurrently with radiotherapy, consolidation chemotherapy was given with doxorubicin, cyclophosphamide, methotrexate, and etoposide. The complete response rate was 35% for ED patients and 68% for LD patients. The median survival time for complete responders was 54 weeks for ED patients and 65 weeks for LD patients. The toxicity of the program was moderate, and the effectiveness was comparable to that of other reported combined-modality treatment programs.

Adult↗
PubMed1982

Extracellular paraprotein globules in a patient with monoclonal gammopathy.

A patient with a plasma cell disorder and IgA lambda paraprotein had the unusual finding of numerous, large, opaque, extracellular globules in her bone marrow and liver. While plasma cell intracellular inclusions are well documented, identification of such material in extracellular sites is not. These globules were of various sizes, stained light to dark blue with Wright's stain, were gray in hematoxylin-eosin preparations, and were fluorescent when stained with conjugated antibodies to lambda, but not to kappa, light chains. They strongly resembled the inclusions (Russell bodies) seen in plasma cells and are believed to be massive accumulations of immunoglobulin. The clinical significance of this morphological finding is unknown, but physicians interpreting bone marrow specimens should be aware of this unusual feature.

Aged↗
PubMed1982

Murine monoclonal antibody therapy in two patients with chronic lymphocytic leukemia.

We infused the murine monoclonal antibody T101 into two patients with advanced refractory chronic lymphocytic leukemia (CLL) after confirming its reactivity with their CLL cells. One patient received doses of 1, 3, and 12 mg; the second patient received 10 mg. Antibody was delivered over 10--15 min. The major observations were: (1) T101 murine monoclonal antibody did bind to cells with T65 surface antigen and saturated these cells in vivo; (2) cells that bound T101 disappeared from the circulation by 2 hr after treatment, as evidenced by a marked drop in lymphocyte counts; (3) T101 serotherapy resulted in some intravascular cell injury associated with sequestration and probably destruction in the liver and lung; (4) free serum T101 was demonstrable, but disappeared by 2--4 hr after infusion; (5) rapid infusion of T101 did not induce significant modulation of T65; (6) rapid infusion of greater than 10 mg of T101 was associated with significant systemic reactions. Monoclonal antibodies may someday have an application in leukemia therapy, but additional experimental trials are clearly indicated.

Antibodies, Monoclonal↗
PubMed1981

Alterations of peripheral blood B-lymphocyte populations in plasma cell disorders.

Peripheral blood lymphocytes of patients with multiple myeloma, macroglobulinemia, and monoclonal gammopathy of uncertain significance were analyzed for B cells, and cells bearing kappa light chains and lambda light chains on their surfaces. Compared with controls, the number of B cells were decreased in all three groups. Contrary to other reports, the authors found a B-cell depression of similar magnitude in patients with untreated myeloma and in those with apparently benign monoclonal gammopathy. There was no difference between treated and untreated myeloma patients as a group, or as individuals studied before and after treatment. However, in comparison to control patients, alkylator therapy depressed the leukocyte count, lymphocyte count, and B-cell number both in the myeloma and in the macroglobulinemia groups. All five patients with previously untreated macroglobulinemia had an increased proportion of circulating lymphocytes with surface light chains of the same type as the M protein. Two patients with IgG myeloma-like disorders had increased circulating B cells with monoclonal surface light chains. This study supports the concepts that normal B cells are depressed in plasma cell disorders, and that abnormal B cells, which are apparently monoclonal, do circulate in some cases. Our results are compared with other published data.

Aged↗
PubMed1981

Plasma calcitonin as a marker of disease activity in patients with small cell carcinoma of the lung.

To evaluate the usefulness of plasma calcitonin as an index of tumor burden and disease activity, we undertook a prospective study of serial calcitonin measurements in a group of patients with small cell carcinoma of the lung from diagnosis throughout a period of intensive therapy. Plasma calcitonin was significantly elevated in 84% of patients with extensive small cell carcinoma of the lung and was not elevated in patients with limited disease at the time of diagnosis. The elevated values fell significantly in response to chemotherapy and radiation therapy, and reflected regression of followable disease and improvement in clinical status. A significant correlation existed between plasma calcitonin and extent of disease. Relapse was generally associated with an increase in elevated plasma calcitonin levels, and calcitonin appeared to reflect tumor burden. The serial measurement of plasma calcitonin is useful in the management of the patient with small cell carcinoma of the lung.

Calcitonin↗
PubMed1981

Comparative density of the human T-cell antigen T65 on normal peripheral blood T cells and chronic lymphocytic leukemia cells.

A 65,000 dalton T-cell specific antigen previously demonstrated to be present on the surface of normal and malignant T cells, but not normal B cells, has been detected on the surface of leukemic cells from patients wih nonsecretory, surface immunoglobulin-positive chronic lymphocytic leukemia (CLL). By means of immunofluorescence and flow cytometry, the relative surface density of the T65 antigen on CLL cells was compared to that on normal peripheral blood T cells and human thymocytes, as well as cell lines of T-cell lineage. In all cases, the CLL cells had a more homogeneous and a lower median fluorescence intensity than that of normal circulating T cells. Thymocytes were composed of three populations, two with low surface density of T65 resembling the CLL cells and the other with higher density similar to normal T cells. The staining of cell lines varied from bright, heterogeneous staining (8402) to uniform, low-density staining (Molt-4). The implications of these findings with regard to lymphocyte differentiation are discussed.

Animals↗
PubMed1980

Human T-cell antigens defined by monoclonal antibodies. Absence of T65 on committed myeloid and erythroid progenitors.

The complement-dependent cytotoxicity of monoclonal T-cell antibody (T101) for normal and abnormal hemopoietic progenitors was assessed. T101 demonstrated toxicity for normal T-colony-forming cells from peripheral blood and bone marrow. Cytotoxicity was absent for normal peripheral blood and bone marrow granulocytes/macrophage (CFU-C) and erythroid (BFU-E) progenitors. The antibody was also not toxic for peripheral blood blast progenitors from patients with acute myelogenous leukemia (AML). These studies indicate the absence of the antigen defined by T101 (T65) from normal progenitor cells and from blast progenitors in patients with AML. T101 may be used in the treatment of T-cell malignancies and in the prevention of graft-versus-host disease (GVHD) without damage to normal progenitor cells.

Antibodies↗